tbuckley/cabot-search huggingface dataset:
Genotype matched treatment for patients with advanced type I epithelial ovarian cancer (EOC).
Authors: Anna Spreafico, Amit M. Oza, Blaise Clarke, Helen Mackay, Patricia Shaw, Golnar Rasty, Marcus O. Butler, Neesha C. Dhani, Stephanie Lheureux, Michelle Wilson, Stephen Welch, Lillian L. Siu, Tong Zhang, Celeste Yu, Geeta D Krishna, Helen Chow, Tracy Stockley, Suzanne Kamel-Reid, Philippe L. Bedard
Journal: Journal of Clinical Oncology (2014)

5506 Background: Type I EOCs are uncommon, genetically stable tumors that are often resistant to chemotherapy. Genomic alterations that activate the Mitogen-Activated Protein-Kinase (MAPK) signaling pathway frequently occur in Type I EOCs that may sensitize to downstream MEK inhibition. Methods: Formalin fixed paraffin embedded tumor tissues from patients (pts) with Type I EOC were prospectively screened for genomic alterations in a CLIA-certified laboratory using Sequenom MassArray genotyping or targeted sequencing using the Illumina MiSeq TruSeq Amplicon Cancer Panel. The outcomes of pts receiving treatment at Princess Margaret Cancer Centre were retrospectively reviewed. Results: From Mar/11 to Jan/14, 49 pts with type I EOC underwent molecular testing, including 80% low grade serous (LGS), 10% clear cell (CC), and 10% mucinous (MC) histologies. Thirty-two pts (65%) were found to have ≥1 somatic mutations: 23 KRAS, 6 NRAS, 2 PIK3CA, 1 BRAF, 1 AKT, 1 PTEN, 1 TP53, 1 CTNNB1. Fifteen pts (47%) with a median of 2 (range 0-4) prior systemic therapies were treated on genotype-matched phase I or II trials with targeted inhibitors. Fourteen pts (93%) with KRAS/NRAS mutations (12 LGS, 1 CC, 1 MC) were treated with targeted combinations that include a MEK inhibitor. Best RECIST 1.1 response for the 14 evaluable pts included: 5 PR (4 confirmed), 8 SD and 1 PD. In pts with PR/SD as best response, the median % of target-lesions shrinkage was 27% (range 12.5-62.5%). Gynecological Cancer Intergroup CA125 related-response was observed in 8/8 KRAS and/or NRAS mutant pts treated with MEK inhibitor combination treatments. Of 9 pts who had received prior systemic therapy for recurrent disease, the median duration of genotype-matched treatment was 19 weeks (range 6.5-58), compared with 9 weeks (range 4-53) for the immediate prior line of therapy. Conclusions: Genotyping and targeted sequencing of Type I EOCs frequently identifies actionable mutations. Matched treatment with MEK inhibitors in KRAS and/or NRAS mutant type I EOC pts is an active therapeutic strategy.
Social network, social support and unplanned hospital admission in older patients with cancer.
Authors: Beatrice Jara-Almonte Edwards, Ming Sun, Shuangshuang Fu, Xiaotao Zhang, Christine Markham
Journal: Journal of Clinical Oncology (2017)

201 Background: Cancer incidence is rising as the number of older adults increases. Lack of social support has been found to predict mortality among cancer patients. Emotional support has been reported to be the most desirable type of social support. Methods: The data was collected prospectively, and analysis conducted in a retrospective manner, in a cohort of older adults seen at the Program for Healthy Aging at the MD Anderson Cancer Center between Jan 2013 and December 2015. Demographics, cancer diagnosis, and other geriatric conditions were diagnosed and collected during comprehensive geriatric assessments. Social supports were measured through self-report RAND’s Medical Outcomes study (MOS) questionnaires. Overall social support and sub domains (emotional, informational, tangible, affectionate, and positive interaction) were scored. Outcomes including unplanned hospital admission were collected through reviewing of medical records. Pearson chi-square or the Fisher exact tests were used to compare groups on admission. Logistic regressions were used to investigate the relative contribution of social network and social supports for unplanned hospital admission. Results: Among 132 patients who were included in the analysis, 49(37%) patients had unplanned hospital admissions, and the overall social support score was 86%. Cancer type -hematologic versus solid tumors- demonstrated a stronger association with hospitalizations than social support. The subdomains of tangible support, positive interaction, and affection support were different between two groups. Tangible support had an odd ratio of 10.6 (p = 0.026) in unplanned hospital admission, after adjusting for cancer type, cancer stage, and cognitive status. In our study population, patients who receive more social support were more likely to be hospitalized. Conclusions: Among older cancer patients, those who receive more social support are more likely to be hospitalized. Further studies that correlate with health outcomes may be meaningful to develop strategies or interventions to improve clinical practices, to enhance quality of life and meaningful survival in elderly cancer patients.
Uptake of an Acrochordon Incidentally Detected on 68Ga Prostate-Specific Membrane Antigen PET/CT
Authors: Gozde Daglioz Gorur, Turkay Hekimsoy, Serkan Isgoren, Aysun Sikar Akturk, Hakan Demir
Journal: Clinical Nuclear Medicine (2017)

68Ga prostate-specific membrane antigen (PSMA) PET/CT is a promising tool for imaging of prostate cancer. 68Ga-PSMA PET/CT uptake of prostate cancer and its metastases are reflective of significant overexpression of PSMA. However, PSMA expression of benign neoplasms and nonprostate epithelial malignancies is not very well defined. We report a moderate 68Ga-PSMA uptake of an acrochordon (skin tag), which was incidentally found in a patient referred for staging prostate cancer. Acrochordon is a frequent, small, soft, skin-colored or hyperpigmented, benign, and usually pedunculated neoplasm of the skin. Nuclear medicine physicians should be aware of it while reporting a 68Ga-PSMA PET/CT.
Association of the prostate cancer risk mutation G84E in HOXB13 with the subtype of ETS fusion negative adenocarcinoma with early age of diagnosis.
Authors: Thomas J. Schnoeller, Manuel Luedeke, Antje Rinckleb, Janet L. Stanford, Liesel Fitzgerald, Johanna Schleutker, Tiina Wahlfors, Ros A. Eeles, Zsofia Kote-Jarai, Steffen Weikert, Hans Krause, Kathleen Herkommer, Josef Hoegel, Christiane Maier
Journal: Journal of Clinical Oncology (2015)

5021 Background: HOXB13 was discovered as the first prostate cancer (PrCa) specific high-risk susceptibility gene. The most prevalent HOXB13 germline mutation in PrCa patients of European descent is HOXB13G84E, which likely originated in Northern Europe. Previous molecular examination of a set of G84E driven tumors suggested a distinct somatic phenotype, where oncogenic ETS gene fusions appear at unusually low frequencies as compared to the general prevalence of ETS fusions in PrCa (22 % vs approx. 50 %). Methods: We have analyzed 942 cases from three European ancestry populations for the coincidence of HOXB13 G84E and the most common ETS fusion, TMPRSS2-ERG(T2E), in corresponding tumor samples. Results: While the prevalence of T2E fusions was similar among study sites (range: 56.5% - 60.7%), the frequency of G84E genotypes differed markedly between US (1.5%), German (3.6%) and Finnish samples (8.3%). Despite the expected frequency gradient among study populations, all subsamples showed a strong enrichment of G84E mutation carriers among T2E fusion negative cases as compared to fusion positive cases (center adjusted OR = 4.90; 95%CI = 2.19 - 11.0; p = 0.0001). Consistent with the previous study, the crude frequency of the T2E fusion in HOXB13G84E carriers was 23.5 % (range 16.7 % - 28.5 %). Examination of disease characteristics highlighted age at diagnosis, with fusion positive cases being diagnosed 1.75 (0.87 - 2.63) years earlier than negative cases (p < 0.0001). Age at diagnosis in G84E carriers did not differ significantly from non-carriers (p = 0.26). However, within the subtype of fusion negative carcinoma, which is usually associated with later ages at diagnosis, carriers of G84E were diagnosed on average 2.93 (0.49 - 5.37) years earlier (p = 0.02). No associations were seen for tumor stage, tumor grade or diagnostic PSA levels. Conclusions: This study demonstrated a tumor type specific association for HOXB13 G84E mutation carriers having a higher frequency of T2E fusion negative PrCa. Although the T2E fusion negative subtype is known to be associated with later ages of diagnosis, HOXB13 driven tumors within this subtype may represent an early onset subgroup.
An Official American Thoracic Society/European Respiratory Society Statement: Asthma Control and Exacerbations
Authors: Helen K. Reddel, D. Robin Taylor, Eric D. Bateman, Louis-Philippe Boulet, Homer A. Boushey, William W. Busse, Thomas B. Casale, Pascal Chanez, Paul L. Enright, Peter G. Gibson, Johan C. de Jongste, Huib A. M. Kerstjens, Stephen C. Lazarus, Mark L. Levy, Paul M. O'Byrne, Martyn R. Partridge, Ian D. Pavord, Malcolm R. Sears, Peter J. Sterk, Stuart W. Stoloff, Sean D. Sullivan, Stanley J. Szefler, Mike D. Thomas, Sally E. Wenzel
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways.The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older.A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures.The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge about the multiple domains of asthma and asthma control, no single outcome measure can adequately assess asthma control. Its assessment in clinical trials and in clinical practice should include components relevant to both of the goals of asthma treatment, namely achievement of best possible clinical control and reduction of future risk of adverse outcomes. Recommendations are provided for the assessment of asthma control in clinical trials and clinical practice, both at baseline and in the assessment of treatment response.The Task Force recommendations provide a basis for a multicomponent assessment of asthma by clinicians, researchers, and other relevant groups in the design, conduct, and evaluation of clinical trials, and in clinical practice.
Impact of race on gastric adenocarcinoma outcomes in a multiracial population.
Authors: Jared David Acoba, Nicholas E Simon
Journal: Journal of Clinical Oncology (2017)

196 Background: Gastric adenocarcinoma continues to be a major health issue, with a high prevalence among Asian and Pacific Islander populations. We performed a comprehensive analysis to evaluate outcomes and prognostic factors in a multiracial population with a focus on Whites, Asians (Chinese, Japanese, Koreans, Filipinos), and Pacific Islanders (Native Hawaiians, Samoans). Methods: We collected data from 615 consecutive patients with gastric or gastroesophageal adenocarcinoma diagnosed between 2000 and 2015. Multivariable Cox proportional hazards regression models for survival were built adjusting for race, age at diagnosis, stage, number of lymph nodes resected, histologic grade, HER2 status, systemic treatment, and insurance status for the entire study population and for those with resectable cancer. Results: Pacific Islanders presented at a younger age, higher stage, and more often were underinsured. White patients were more often diagnosed with proximal tumors. Analysis of the entire population demonstrated that older age, underinsured status, higher tumor grade, and advanced stage but not race were poor prognostic factors. Among patients with resectable cancers, the Filipino and Samoan racial sub-groups were adversely associated with survival even after adjusting for other prognostic factors. Furthermore, among Asians, Filipinos had worse outcomes compared with other Asian sub-groups. Overall, 9.5% of the 118 tumors tested for HER2 were deemed HER2(+), however the rate varied by race being as high as 43% among Samoans. Conclusions: No racial survival disparity was detected for gastric and gastroesophageal adenocarcinoma, however among resectable and potentially curable patients, Filipinos and Samoans fared worse. This could be in part due to differences in tumor biology such as HER2 expression. Further study in this area should be pursued. Within the Asian race, Filipinos demonstrated poorer survival than other sub-groups. Given the differences in survival within the Asian race, studies exploring the relationship between race and cancer should consider analysis by sub-group.
Using a combination of plasma and urine biomarkers along with serum PSA in predicting prostate cancer and screening for high-risk cancer.
Authors: Maher Albitar, Wanlong Ma, Ferras S. Albitar, Kevin Diep, Herbert A. Fritsche, Neal D. Shore
Journal: Journal of Clinical Oncology (2014)

e16026 Background: We have previously reported algorithms which combine urine and plasma biomarkers to provide diagnostic information regarding a decision to perform a prostate biopsy and biologic stratification of aggressive prostate cancer (PCa). We expanded our biomarker panel to explore the potential of incorporating androgen receptor (AR) and PTEN expression levels in urine and plasma to improve our algorithms’ ability to: 1) Determine the presence of PCa in patients with presumed benign prostate hyperplasia (BPH), and to:2) Distinguish high- vs. low risk PCa. Methods: We measured the mRNA levels of UAP1, PDLIM5, IMPDH2, HSPD1, PCA3, PSA, TMPRSS2, ERG, GAPDH, B2M, AR, and PTEN in plasma and urine. Patient age, serum PSA (sPSA) level, and PCR data were used to develop algorithms. Gleason Score (GS) <7 is used as the indicator for low-risk PCa. Approximately two thirds of patients (190/287) were used as the training set. Results: In a cohort of 287 patients undergoing prostate biopsy, results demonstrated that 103 (36%) showed BPH and 184 (64%) had PCa. Of these patients with PCa, 107 (58%) had high-risk PCa (GS≥7). Using our biomarker algorithm, the area under the receiver operating characteristic curve (AUROC) for distinguishing PCa from BPH was 0.87. The model sensitivity was 76% and specificity of 71%, using the testing set. A 2ndalgorithm for predicting high-risk PCa (GS ≥7) vs. GS <7 cancer or BPH demonstrated an AUROC of 0.80. This algorithm demonstrated a specificity of 76% and a sensitivity of 44% in the testing set. Patients with concordant results showed specificity of 89% and sensitivity of 59% for having high-grade aggressive PCa, and specificity of 94% and sensitivity of 81% for having PCa and not BPH, but with tolerating the non-detection of low-risk PCa. Combining the two algorithms and accepting a diagnosis of PCa if one of the two algorithms was positive for cancer, regardless of the aggressiveness, showed specificity and sensitivity of 82% and 92% respectively, with the possibility of missing low-risk cancer. Conclusions: Adding AR and PTEN to other biomarkers can significantly improve the value of serum PSA in predicting and screening for PCa as well as detecting high-risk PCa.
378. Normalization and Accelerated Stabilization of VEGF-Induced Angiogenesis by Co-Delivery of Engineered PDGF-BB and VEGF Proteins From Fibrin Matrices
Journal: Molecular Therapy (2014)

Reference EPFL-CONF-201376Afficher la publication dans Web of Science Notice creee le 2014-08-29, modifiee le 2017-05-12
Molecular dissection of primary mediastinal germ cell tumors.
Authors: Lucia Nappi, Matti Annala, Gillian Vandekerkhove, Ladan Fazli, Martin Gleave, Kim N. Chi, Christian K. Kollmannsberger, Alexander William Wyatt
Journal: Journal of Clinical Oncology (2017)

417 Background: Mediastinal non-seminomas (M-NS) have a poor prognosis compared to non-M-NS germ cell tumours (GCT) (i.e. primary gonadal or mediastinal seminomas (PG-S and M-S) and primary gonadal non-seminoma (PG-NS). M-NS tumors, while having pathological and serological similarity to other nonseminomas, are clinically and biological distinct and are considered IGCCC poor risk. In this study we aimed to evaluate the somatic mutation rate and prevalence of actionable/informative mutations in M-NS compared to M-S and primary GCT to inform consideration of targeted/precision therapy in these patients. Methods: Pre-treatment formalin fixed paraffin embedded specimens were collected from eleven patients with mediastinal and primary GCT patients (4 M-NS, 2 M-S, 3 PG-NS and 2 PG-S). High-density tumor areas were selected for DNA extraction and targeted sequencing of 578 established pan-cancer genes was performed (Roche Nimblegen SeqCaP EZ Comprehensive Cancer Design). Results: Consistent with the known landscape of testicular cancer, we identified five tumors with amplification of chromosome 12p, as well as hotspot mutations in KIT (n = 2) and KRAS (n = 1). Three of the 4 M-NS tumors had a non-synonymous mutation rate &gt; 1 per Mb, which is higher than the primary TGCT and M-S sequenced here (range 0-0.5 per Mb) and the established low mutation rate for TGCT of 0.3-0.9 mutations/Mb. Mutations in TP53 (n = 2) and PTEN (n = 1) were only identified in patients with M-NS. The 2 patients with a TP53 mutation had a high non-synonymous mutation rate (1.3/Mb and 7.3/Mb), extensive metastatic disease with liver metastasis and high tumor markers (β-HCG: 1281 IU/L and α-FPT: 8500 ng/ml) at diagnosis. Both died of their disease and were the only patients in the cohort to have died. Conclusions: This study suggests that M-NS GCTs harbour more somatic alterations than non-M-NS GCTs, potentially underlying their poor prognosis. Our data are consistent with previous reports of an association between TP53 mutations and poor outcomes. Confirmation of our findings could lead to multi-center studies of targeted/precision therapies in patients with M-NS.
Incidence and characterization of antiandrogen withdrawal syndrome (AAWS) after enzalutamide (ENZA) in patients (pts) with metastatic castration-refractory prostate cancer (mCRPC).
Authors: Austin Poole, David Michael Gill, Andrew W. Hahn, Eric Johnson, Emma Carroll, Julia A. Batten, Sumati Gupta, Kenneth M. Boucher, Benjamin Louis Maughan, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2017)

228 Background: AAWS manifested as PSA decline after discontinuation of first generation AAs, like bicalutamide, has been well characterized and reported. Objective of this study was to assess the incidence and characterize AAWS after ENZA in pts with mCRPC. Methods: From a single institution cohort, pts with mCRPC who discontinued ENZA after documented disease progression per PCWG2 criteria were included. AAWS after ENZA was defined as any degree of PSA decline after discontinuation of ENZA. Baseline pts, disease, and treatment characteristics were compared between Òpts with AAWS after ENZAÓ vs. Òpts without AAWS after ENZAÓ treated during the similar time period: median values were compared with the Wilcoxon rank sum test; proportions were compared with FisherÕs Exact test; and the log rank test was used to compare PFS (Table). Results: 5 pts of 72 eligible pts (~7%) experienced AAWS after discontinuation of ENZA. The levels of PSA decline were as follows: 84%, 32%, 17%, 15% and 15%, respectively. Median AAWS response time, until subsequent PSA progression, was 6 weeks. None of the pts, disease or treatment characteristics (such as prior duration of response to ENZA) were different among Òpts with AAWS after ENZAÓ vs. Òpts without AAWS after ENZAÓ. Conclusions: This is the largest study reporting on the incidence and characterization of AAWS after ENZA. AAWS after ENZA is infrequent (~7%), of short duration (6 weeks), and not predicted by pts, disease or treatment related characteristics. Unlike AAWS after first generation AR inhibitors, like bicalutamide, the AAWS after ENZA is not clinically meaningful and should not have any bearing on the eligibility criteria of clinical trials conducted in the post ENZA setting. [Table: see text]
PD-L1 expression and genotype in non-small cell lung cancer (NSCLC).
Authors: Sascha Ansen, Anne Maria Schultheis, Martin Hellmich, Thomas Zander, Michael Brockmann, Erich Stoelben, Harry J.M. Groen, Wim Timens, Reinhard Buettner, Roman K. Thomas, Sven Perner, Juergen Wolf
Journal: Journal of Clinical Oncology (2014)

7517 Background: Tumor cells expressing programmed cell death 1 ligand (PD-L1) are believed to suppress immune responses through activation of the PD-1/PD-L1 pathway. Recent data indicate that PD-L1 tumor status might be predictive for responses to PD-1- and PD-L1- directed therapies. Methods: PD-L1 expression was evaluated in genomically annotated 259 adenocarcinomas (AD) and 180 squamous cell carcinomas of the lung (SQ) using immunohistochemistry (IHC). Moreover, PD-L1 expression and its correlation with clinical data, histology and genotype were analyzed. Results: Tumors were considered PD-L1 positive if tumor cells showed at least weak membranous staining by IHC. 83 of 259 patients (pts.) with AD were positive for PD-L1 surface expression (=32,0%). The observed staining intensity was weak, intermediate and strong in 38, 33 and 12 cases respectively. 55 of 180 pts. with SQ were PD-L1+(=30,6%). The observed staining intensity was weak, intermediate and strong in 27, 21 and 7 cases respectively. For AD and SQ no significant association between PD-L1 expression and clinical characteristics (gender, smoking history, stage) could be found. PD-L1 expression in AD or SQ was not significantly associated with ALK translocation (n=178; n=138), BRAF mutation (mut.) (n=113; n=98), DDR2 mut. (n=59; n=64), EGFR mut. (n=124; n=101), FGFR2 mut. (n= 117; n=91), HRAS mut. (n=94; n=73), KRAS mut. (SQ, n=101), NFE2L2_exon2 mut. (AD, n=97), NRAS mut. (n=109; n=81), PIK3CA mut. (n=121; n=99), STK11 mut. (SQ, n=101), TP53 mut. (n=124; n=101) or RB1 deletion (SQ, n=109). However, PD-L1 expression in AD is significantly more frequent in KRAS mutated than in KRAS wild-type samples (n=126; p=0,002) and significantly more frequent in samples with deletion of RB1 (n=143; p=0,024). On the contrary, PD-L1 expression in AD is significantly less frequent in samples with STK11 mutations (n=122; p=0,022). Finally, PD-L1 expression in SQ is significantly more frequent in samples with a mutation in exon 2 of NFE2L2 (n=88; p=0,025). Conclusions: PD-L1 expression in the two most common histological NSCLC subtypes is associated with distinct genotypes that might further facilitate identification of pts. most suitable for therapeutic anti PD-1 and anti PD-L1 intervention.