tbuckley/cabot-search huggingface dataset:
Impact of p16 expression on induction taxotere-cisplatin-5 FU (TPF) followed by cetuximab-radiotherapy in N2b-N3 head and neck squamous cell carcinoma (HNSCC): Results of GORTEC 2007-02 phase III randomized trial.
Authors: Yungan Tao, Lionnel Geoffrois, Laurent Martin, Dominique De Raucourt, Joelle Miny, Philippe Maingon, Cedrik Lafond, Claude Tuchais, Christian Sire, Emmanuel Babin, Alexandre Coutte, Frederic Rolland, Marie-Helene Girard-Calais, Odile Casiraghi, Pascal Garaud, Jean Bourhis
Journal: Journal of Clinical Oncology (2017)

6070 Background: TPF is a reference induction chemotherapy regimen in non-operated locally advanced (LA) HNSCC. GORTEC 2007-02 phase III randomized trial was restricted to HNSCC patients with large nodal spread (N2b-N3). Results showed no benefit of 3 cycles of induction TPF followed by cetuximab-radiotherapy (RT), as compared to concurrent chemoradiotherapy (CRT) (Geoffrois et al ASCO 2016). Methods: Patients were randomized to receive concurrent CRT (arm A) or induction TPF followed by cetuximab-RT (arm B). RT was 70 Gy/35F/7 weeks. Concurrent chemotherapy was 3 cycles of carboplatin-5FU as previously described (Calais JNCI 1999). About 2/3 of patients had oropharyngeal cancers (OPC) and HPV status was determined in these patients using p16 expression as a surrogate (immunohistochemistry). Smoking status was also collected. Primary endpoint was progression free survival (PFS). Results: Between May 2009 and Aug 2013, 360 eligible patients were randomized including 231 (64%) OPC. Overall, p16 expression could be assessed in 172 / 231 OPC patients (74%) with 84 in arm A and 88 in arm B. 26 patients were found p16+ in arm A (31%) and 19 in arm B (22%). Only 8 out 45 (18%) p16+ patients were non-smokers showing that the large majority of OPC patients randomized were p16- (127/172) and smokers (117/129). A significant improvement in PFS was found in p16+ compared to p16- OPC (p &lt; 0.0001). The absence of benefit in PFS associated with TPF + cetux-RT compared with CRT was suggested both in p16+ (HR: 0.78, 95% CI: 0.28 – 2.20) and in p16- OPC (HR: 1.28, 95% CI: 0.84 – 1.93), and the interaction between p16 and treatment modality was not significant (p = 0.35). A significant benefit was observed in favor of arm B regarding distant metastasis, but this effect was not different between the p16+ and p16- OPC, while there was no benefit of TPF + cetux-RT compared with CRT for loco-regional control, regardless of p16 status. Conclusions: The OPC p16 subpopulations were small. No benefit of induction TPF chemotherapy followed by cetuximab-RT compared with CRT in OPC patients regardless of p16 status. Clinical trial information: NCT01233843.
Cisplatin (CIS) versus cetuximab (CET) with definitive concurrent radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC): An analysis of veteran’s health data.
Authors: Joshua Bauml, Ravi R. Vinnakota, Yeun-Hee Anna Park, Susan Elaine Bates, Antonio Tito Fojo, Charu Aggarwal, Jessica DiStefano, Christina Knepley, Eric Michael Genden, Sewanti Atul Limaye, Christine Agnes Ciunci, Juan P. Wisnivesky, Nevena Damjanov, Corey J. Langer, Roger B. Cohen, Keith Sigel
Journal: Journal of Clinical Oncology (2018)

6073 Background: The addition of CIS or CET to RT improves outcomes compared to RT alone in the non-operative management of HNSCC, but limited data exist on the comparative effectiveness and safety of these approaches. We compared outcomes of pts treated with RT plus CIS or CET using population-based Veterans Health Administration (VHA) data. Methods: We identified stage III-IVb HNSCC patients (pts) treated non-surgically with RT and CIS or CET from 2002 to 2014 in the VHA. Pts were analyzed by the drug used in their first cycle (CIS or CET; intent-to-treat). Variables including primary cancer site, age, stage, smoking/alcohol use, and Charlson Comorbidity Index were used to generate propensity scores (PS) for the use of CET. We compared overall survival (OS) by treatment group using Cox regression models, matching for PS. We determined the risk of toxicities using PS-matched logistic regression. Results: A total of 3,986 pts were included in the analysis with a median follow-up of 3 years (yrs): 81% received CIS (19.8% low dose - 30-50 mg/m2). CIS pts were younger (p < 0.001) and had fewer comorbidities (p < 0.001). In an unadjusted analysis, CET was associated with inferior OS (p < 0.001). This remained significant after matching for PS (HR 1.66, 95% CI 1.48-1.86, p < 0.001), corresponding to a median OS of 1.8 vs 4.2 yrs. CET was associated with inferior survival across all primary subsites. CET was associated with inferior survival vs low dose CIS, after PS matching (See Table). Matching for PS, CET was associated with a lower rate of neutropenia, renal failure and hearing loss than CIS (all p < 0.001). Conclusions: CET yields inferior OS compared to CIS with RT for non-operative management of Stage III-IVb HNSCC. Based on this registry study, CIS should remain the preferred partner for RT in this setting. Median OS (yrs) CET CIS HR 95% CI p value Unadjusted [n = 3,986] 1.5 3.8 1.78 1.63-1.95 < 0.001 PS matched [n = 2,114] 1.8 4.2 1.66 1.48-1.86 < 0.001 Oral Cavity (n = 135) 0.8 1.0 1.62 1.07-2.44 0.02 Oropharynx (n = 1,485) 1.0 4.6 1.63 1.42-1.88 < 0.001 Larynx/Hypopharynx (n = 477) 1.4 3.2 1.87 1.49-2.34 < 0.001 Low dose CIS, PS matched [n = 902] 1.6 3.9 1.53 1.30-1.80 < 0.001
Toxicity and efficacy of bolus (BOL) versus continuous intravenous (CIV) dosing of doxorubicin (DOX) in soft tissue sarcoma (STS): Post hoc analysis of a prospective randomized trial.
Authors: Lee D. Cranmer, Yao Lu, Karla V. Ballman, Elizabeth Trice Loggers, Seth Pollack
Journal: Journal of Clinical Oncology (2017)

11023 Background: DOX remains critical in STS treatment. Controversy exists regarding its optimal administration route (BOL vs CIV). BOL vs CIV could affect toxicity and/or efficacy. A randomized trial to assess this is unlikely. We conducted a post hoc analysis to explore differences in these routes of DOX administration. Methods: Data from a prospective randomized phase III study of doxorubicin with or without evofosfamide (TH-302) were used. At the discretion of treating physician, BOL or CIV DOX could be used. Grade 3-5 hematologic, non-hematologic and cardiac toxicities and treatment response were explored using multivariable logistic regression. OS and PFS were analyzed using Kaplan-Meier and Cox proportional hazards. Results: 640 subjects were enrolled (556 BOL, 84 CIV). Baseline differences in age, extent of disease and prior radiotherapy were controlled for in regression models. Hematologic toxicity was associated with age, performance status (PS) and cumulative (CUM) DOX dose. Non-hematologic toxicity was associated with age, PS, receipt of prior radiotherapy and CUM TH-302 dose. Cardiac toxicity was only associated with CUM DOX dose. Odds of response were strongly associated with CUM DOX dose (mg/m 2 , OR = 1.011, p &lt; 0.0001), and, to a lesser extent, with CUM TH-302 dose (g/m 2 , OR = 1.081, p = 0.0008), STS subtype and prior radiotherapy. Comparing CIV to BOL DOX, neither OS (median 21.7m vs 18.3m, HR = 0.85, p = 0.29) nor PFS (median 6.1m vs. 6.1m, HR = 0.89, p = 0.43) was affected by manner of DOX administration (CIV vs BOL). Cox analyses indicated that factors reflecting tumoral biology and host status, rather than treatment received, were associated with OS (PS, histologic STS subtype, histologic grade, receipt of prior radiotherapy) and PFS (PS, treatment-related toxicity). Conclusions: Our analyses provide no evidence for superiority of either BOL or CIV administration of DOX as regards toxicity or efficacy in STS treatment. Thus, the logistically simpler BOL administration of DOX should be favored over CIV administration.
Potential impact of dietary intervention/counseling on survival in ovarian cancer patients: Results from an observational study.
Authors: Jessica Michalak, Mike Hernandez, Alexandria Laws, Lovell Jones, Diane C. Bodurka, Richard Hajek
Journal: Journal of Clinical Oncology (2018)

5541 Background: Ovarian cancer is the fifth leading cause of cancer death in women, and survival rates remain largely unchanged within the past forty years. Previous research suggests that dietary intervention may impact cancer development, prognosis, and survival. The purpose of this study was to determine if dietary intervention was associated with improved survival rates in ovarian cancer patients. Methods: A total of 183 women were enrolled in the cohort study at MD Anderson. Clinical data collected on a cohort of patients who received the dietary intervention including counseling and supplementation were compared to a cohort of contemporary controls and summarized using descriptive statistics. Survival was computed from the time of admission to time of death or loss to follow-up. The method of Kaplan-Meier was used to provide overall survival estimates at select points in time, and the Log-rank test was used to compare survival distributions between cohorts. Results: Estimates of overall survival for intervention (49) and control (125) patients were: 95.9% and 66.8% at 5-years; 87.1% and 34.0% at 10-years; and 76.7% and 22.9% at 15-years, respectively (Log-rank test P-value < .001). Control patients had over four times the risk of death relative to patients receiving intervention after adjusting for age at admission. Conclusions: Dietary intervention/counseling with supplementation may positively impact survival in women diagnosed with ovarian cancer. Although our findings inspire interest, a weakness was the study’s observational nature and the strong potential for confounding. A prospective, appropriately powered randomized clinical trial is warranted to validate these results.
Characterization of tumor microenvironment in extraskeletal myxoid chondrosarcoma (EMC).
Authors: Valentina Indio, Annalisa Astolfi, Giuseppe Tarantino, Milena Urbini, Chiara Castelli, Salvatore Lorenzo Renne, Paola Collini, Alessandro Gronchi, Chiara Colombo, Anna Maria Frezza, Roberta Maestro, Angelo Paolo Dei Tos, Piero Picci, Paolo Giovanni Casali, Andrea Pession, Maria A. Pantaleo, Silvia Stacchiotti
Journal: Journal of Clinical Oncology (2018)

11561 Background: EMC is a rare sarcoma mostly originating from soft tissues. EMC carries a specific translocation, involving NR4A3, which is fused more often with EWSR1 and less frequently with other partners, including TAF15. We investigated EMC tumor microenvironment to define the differential immune-profile of NR4A3-EWSR1 and NR4A3-TAF15 EMC subtypes and to evaluate if EMC could be good candidate to immunotherapy. Methods: RNA-seq was performed on 12 naïve tumors with Illumina technology. The gene expression was quantified and, after normalization, the tool CIBERSORT was adopted to evaluate the presence of 22 hematopoietic population within the tumor-infiltrating environment. Absolute and relative abundance were used to estimate the correlation between infiltrating cell types. Moreover, the EMC immune-profile was comparatively evaluated between two subgroups of EMC based on the rearrangement type EWSR1-NR4A3 (7/12) and TAF15-NR4A3 (5/12). Immunohistochemistry, for CD3, CD20, CD14, CD163, CD56, HLA ABC, PDL1(22C3), and CD1a was performed and scored on available FFPE specimens (3/12). Results: The analysis showed in all cases the existence of gene signatures related to the presence of immune-infiltrate. Globally, M2 macrophages were the most enriched cell type, followed by CD4+ memory resting, and M0 macrophages; B-cell and mast cell were also moderately observed. The correlation analysis showed that the abundance of M2 macrophages negatively correlated with the presence of CD3+ T-cells. Comparative analysis showed that the EMC with TAF15 fusion had a significantly lower level of CD4+ memory resting cells (p = 0.042), lower NK cells and a trend to a higher enrichment of mast cells compared to EWSR1+ EMC. IHC analysis confirmed the presence of an immune-infiltrate, with both a macrophagic and a lymphocytic component. Conclusions: Our results showed that EMC is marked by the presence of a macrophagic and, to a less extent, a CD4+ T cells immuno-infiltrate. Interestingly, the immune-profile differed between the 2 molecular subtypes, highlighting that the high degree of diversity that marks sarcomas is reflected also in their immune-profile. EMC looks to be a potential interesting candidate for immune-therapy.
TCT-404 Takotsubo Syndrome and Oxidative Stress in Women: What Happens to the Clot.
Authors: Daniela Trabattoni, Benedetta Porro, Silvia Barbieri, Viviana Cavalca, Patrizia Amadio, Sonia Eligini, Paolo Olivares, Franco Fabbiocchi, Antonio Bartorelli, None Elena tremoli
Journal: Journal of the American College of Cardiology (2018)
Endocrine therapy for ovarian cancer: A systematic review and meta-analysis of phase II studies.
Authors: Laura Paleari, Nicoletta Provinciali, Matteo Puntoni, Carlotta Defferrari, Martina Di Luca, Franco Gorlero, Andrea De Censi
Journal: Journal of Clinical Oncology (2016)

5554 Background: Hormonal factors play a key role in epithelial ovarian tumorigenesis and steroid receptor expression has been associated with epithelial ovarian cancer (EOC) response and survival in recent studies. However, the degree of activity of endocrine therapy overall and by specific agents in EOC remains unclear. Methods: RECIST objective response rates (ORR) from phase II trials of different endocrine drugs in EOC patients were meta-analyzed. Pooled estimates (PES) from random effects model were calculated according to type of drug, ER and PgR status, tamoxifen dose, year of study and platinum resistance. Results: A total of 35 phase II studies including 1.690 patients were analyzed. Overall, we observed an PES of 37% (95%CI, 0.28-0.46), including stable disease, with any endocrine treatment. Specifically, the PES was 31% (95%CI, 0.23-0.39) for aromatase inhibitors, 40% (95%CI, 0.21-0.58) for tamoxifen, 41% (95%CI, 0.23-0.59) for estro-progestins, 39% (95%CI, 0.25-0.52) for tamoxifen plus progestins, 30% (95%CI, 0.20-0.40) for progestins, 14% (0-0.58) for the anti-androgen flutamide, 50% (95%CI, 0.31-0.69) for tamoxifen plus goserelin, 52% (95%CI, 0.32-0.72) for the ER down regulator fulvestrant, although the last three categories included only one study each. The PES was better in studies including ER+ and/or PgR+ patients only (43%, 95%CI, 0.34-0.52) compared with those with negative (PES = 17%, 95%CI, 0.09-0.24) or mixed (PES = 31% 95%CI, 0.17-0.46) hormone receptors. The PES by tamoxifen dose was 36% (95%CI, 0.16-0.57) and 50% (95%CI, 0.13-0.87) for high ( > 20 mg/day) or low ( < 20 mg/day) doses, respectively. Finally, a slight better PES was noted in the trials including platinum refractory patients (PES = 35%, 95%CI, 0.19-0.50) versus platinum sensitive patients (PES = 43%, 95%CI, 0.3-0.57). There was no evidence for a trend by year of study. Conclusions: The activity of endocrine therapy in advanced EOC looks promising but has not been adequately evaluated in appropriate clinical trials. Given the recent evidence for a prognostic value of hormone receptors in EOC, our findings support the implementation of randomized trials in hormone receptor positive EOC.
Abstract 18256: Inflammation Identifies a Non-Obese Phenotype With Subclinical Atherosclerosis
Authors: Albert Lin, Mary E Lacy, Charles Eaton, Adolfo Correa, Wen-Chih Wu
Journal: Circulation (2016)

Introduction: Variations in atherosclerotic risk among individuals with similar adiposity are poorly understood, especially in African Americans (AA). high-sensitivity C-reactive protein (hsCRP) ma...
Prognostic role of IMP3 expression in nasopharyngeal carcinoma patients.
Authors: Brena Luize Cunha Ferreira, Maria Aparecida Custódio Domingues, Barbara Estefania Lopez, Odair Carlito Michelin, Patricia Bottamedi Ratto, Luiz Agenor Gazzi, Rafael Amaral De Castro, Victor Nakajima, Marcelo Uratani
Journal: Journal of Clinical Oncology (2016)

e23250 Background: The nasopharyngeal carcinoma (NPC) is an aggressive malignant epithelial neoplasm, presenting a unique behavior of growth and relapse. Despite advances in treatment, NPC has a great need of feasible and cost effective biomarkers to find it’s prognostic behavior, tailor therapies and improve outcomes. The objectives were to measure the expression of IMP3 biomarker, a insulin-like growth factor 2 mRNA binding protein, in patients with NPC, and correlate the rate of expression to the overall survival/clinical outcome of patients. Methods: 35 cases of NPC which occurred between 1999 and 2009 that underwent radiation therapy/combined treatment, were compiled and documented based on their morphological features. The immunohistochemical expression of IMP3 was measured based on intensity and extension, and then correlated with the several clinical-pathologic parameters. Survival rates were analyzed using the Kaplan-Meier study, comparing differences between curves via Log-Rank test. Results: Of the identified histologies, undifferentiated nonkeratinizing nasopharyngeal carcinoma had higher prevalence (26 patients-74,3%). The positivity of IMP3 was observed in 27 patients (86%), with intensity 3+ (34,3%), 2+ (20,0%), 1+ (22,9%); extension 3+ (17,1%), 2+ (37,1%) and 1+ (22,9%). The presence of expression was similar throughout parameters of age, gender, histology and TNM stage. Among 17 patients with undifferentiated nonkeratinizing carcinoma that exceeded 2 years of overall survival, the IMP3 expression was 100% positive, showing a significant tendency of correlation between survival and IMP3 positivity of different rates of intensity and extension (p = 0.007). Conclusions: The immunohistochemical positivity of IMP3 shows a growing trend of correlation to better outcomes in NPC patients. This data shows higher understanding of IMP3 as a biomarker, providing simple and cost effective means of prognosis in nasopharynx carcinoma. More studies with a broader sample population are needed.
Abstract 11938: Risk Factors for Subarachnoid Hemorrhage
Authors: Johan Sundstrom, Bodil Svennblad, Martin Söderholm, Stefan Söderberg, Maria Eriksson, Mauricio Malfert, Susanne Heller, Gunnar Engström, Bernice Wiberg
Journal: Circulation (2016)

Introduction: Subarachnoid hemorrhage (SAH) is a devastating disease, with a high mortality rate and significant disability among survivors. Its causes are poorly understood. Hypothesis: We aimed to investigate risk factors for SAH using an adequately powered novel nationwide cohort consortium with uniform collection of clinical outcomes. Methods: We obtained individual participant data of 949,683 persons (330,334 women) who were between 25 and 90 years old and had no history of SAH at baseline, from 21 population-based cohorts collected during more than 50 years and geographically covering entire Sweden. Outcomes were obtained from the Swedish Hospital Discharge and Causes of Death Registries. Results: During 13,704,959 person-years of follow up, 2,659 first-ever fatal or non-fatal SAH instances were observed. In Poisson regression models with random effects for the cohort level, referencing the population distribution in Sweden year 2010, we observed an age-standardized incidence rate of 9.0 (95% confidence interval 7.4-10.6)/100,000 person-years in men and 13.8 (11.4-16.2)/100,000 person-years in women; rate ratio (RR) 1.45 (1.32 to 1.61) for women vs. men. The incidence rate increased exponentially with higher age, with a plateau of similar risk between ages 55 and 75. The RR was 8.28 (4.39 to 15.63) for age-group 85-89 vs. 25-29 years. Lower education level was associated with higher risk, RR 1.56 (1.27 to 1.96) for primary education vs. post-secondary education. Smoking was associated with a markedly increased risk, with an interaction between smoking and sex. Smoking conferred a RR of 1.66 (1.49 to 1.85) in men, and 2.63 (2.27 to 3.05) in women (p&lt;0.01 for interaction). Hypertension was associated with a RR of 1.33 (1.22 to 1.45) for SAH. Several other risk factors were investigated. Conclusions: In this large population-based study, a nearly 50% higher risk of SAH was observed in women than in men. Besides higher age, smoking was the most powerful risk factor for SAH, with a markedly stronger effect in women than in men. Lower education was also linked to higher risk.
LMTK3 as a novel regulator of oncogenic KIT in KIT-mutant cancers.
Authors: Lillian Rose Klug, Jeffrey Tyner, Michael C. Heinrich
Journal: Journal of Clinical Oncology (2017)

11044 Background: Multiple cancers, such as gastrointestinal stromal tumors (GIST) and melanoma, have been shown to be caused by somatic activating mutations in the receptor tyrosine kinase KIT. The major cause of death in patients with advanced KIT -mutant cancers is due to the development of KIT tyrosine kinase inhibitor-resistant (TKI-resistant) metastatic disease. Drug resistance arises almost exclusively from secondary mutations within KIT, highlighting the importance of KIT in the proliferation and survival of these tumors. Methods: We performed a human kinase siRNA screen in multiple KIT -mutant cancer cell lines using viability as a read out. We defined candidate targets as those whose knockdown decreased viability in all cell lines. Validation and mechanistic studies were done using a library of KIT-mutant GIST and melanoma cells. Results: We identified lemur tyrosine kinase 3 (LMTK3) as candidate target in three KIT -mutant cell lines. LMTK3 silencing reduced the viability of all KIT -mutant GIST and melanoma cells tested to date, including cell lines with KIT TKI-resistance mutations. Importantly, LMTK3 silencing decreased the viability of KIT -mutant cells specifically, but not that of KIT-independent GIST and melanoma cells. Further, we found that decreased cell viability was due to induction of apoptosis, as assessed by measuring caspase 3 and 7 activity within 96 hours of LMTK3 silencing. LMTK3 knockdown also reduced tumor growth in vivo in a GIST xenograft model. Because these cells depend so heavily on KIT and the loss of KIT signaling results in cell death, we hypothesized that LMTK3 silencing may affect this pathway. Indeed, LMTK3 silencing decreased levels of autophosphorylated KIT. We also observed a significant decrease in total KIT protein expression. This phenotype and corresponding viability was rescued with exogenous expression of full length LMTK3. Conclusions: LMTK3 is an important regulator of oncogenic KIT expression and activity in KIT-mutant GIST and melanoma and represents a novel, tractable target.
Tolerability of iobitridol in patients with non‐immediate hypersensitivity reactions to iodinated contrast media
Authors: Maria Teresa Gracia‐Bara, Esther Moreno, Elena Laffond, Francisco Muñoz‐Bellido, Milagros Lázaro, Eva Macías, Sonia de Arriba, Valle Campanón, Miriam Sobrino, Ignacio Dávila
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.