tbuckley/cabot-search huggingface dataset:
Association of undetectable PSA with time to metastasis and survival after short-course androgen deprivation therapy for biochemically-recurrent prostate cancer patients.
Authors: Evan Y. Yu, Roman Gulati, Serge Aleshin-Guendel, Heather H. Cheng, Agnes M. Gawne, Jonathan T. Wingate, Ruth Douglas Etzioni, Daniel M. Lim
Journal: Journal of Clinical Oncology (2018)

e17073 Background: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Durable undetectable prostate-specific antigen (PSA) levels are being used in ongoing trials as a marker of efficacy. The clinical relevance of patients with a prolonged undetectable PSA after short course androgen deprivation therapy (ADT) is uncertain. Methods: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6–12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥0.2 ng/mL and no radiographically detectable metastasis. Proportions of patients with undetectable PSA 12 and 24 months after ending ADT were compared to a hypothesized 5% rate using exact binomial tests. Associations with patient and tumor characteristics were examined using logistic regression, and associations with risk of subsequent metastasis and death were evaluated by log-rank tests. Results: After ineligibility exclusions, 23/93 (24.7%; 95% CI 16.4–34.8%; P < 0.001) and 14/93 (15.1%; 95% CI 8.5–24.0%; P < 0.001) of patients had undetectable PSA 12 and 24 months after ending ADT, respectively. Being 1 year older at diagnosis was associated with a 14% (95% CI 5.1–23.7%; P = 0.006) decrease in the odds of detectable PSA after controlling for PSA at diagnosis, PSA doubling time, Gleason sum and time from initial therapy to BCR. Detectable PSA at 12 months was associated with increased risk of metastasis (P = 0.006), prostate cancer-specific death (P = 0.028) and death from any cause (P = 0.065). Conclusions: This single-institution retrospective analysis shows that it is not uncommon to have undetectable PSA 12 or 24 months after a short course of ADT, and this finding correlates with lower risk of metastasis and prostate cancer-specific death. No baseline prognostic characteristic other than age was associated with a durable undetectable PSA. Because of association with lower risks of metastasis and prostate cancer-specific death, it may be reasonable to consider undetectable PSA as a clinical trial endpoint.
State of the Science on Pediatric Mild Traumatic Brain Injury
Authors: Michael McCrea, Geoff Manley
Journal: JAMA Pediatrics (2018)

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Abstract 18391: Birth at 39-40 Weeks Gestation is Associated With Improved Survival in Neonates Supported With Post-Operative Extracorporeal Life Support for Congenital Heart Disease
Authors: Jane McKenzie, Thomas Scodellaro, Yves d’Udekem, Warwick Butt, Siva Namachivayam
Journal: Circulation (2016)

Introduction: The neonatal population compared to other age groups with congenital heart disease (CHD) is unique because of their developmental immaturity, case complexity and consequent higher rat...
Development of non-hematological adverse events in apatinib-treated gastric cancer and their association with clinical outcome: Results from a phase IV study.
Authors: Yi Ba, Jin Li, Shukui Qin, Lu Wen, Wenying Deng, Guifang Zhang, Tongfu Jia, Haijun Zhong, Jianwei Yang, Xiaoyan Lin, Yu-Xian Bai, Yifu He, Zhong Xie, Tienan Yi, Xiangyuan Wu, Feng Ye, Likun Liu, Yong Huang, Mei Wang, Junsheng Wang
Journal: Journal of Clinical Oncology (2018)

4039 Background: Ahead-G201, a multicenter Phase IV study, is conducting to evaluate apatinib as third-line or beyond therapy in a routine practice setting of gastric cancer patients (pts). Methods: This analysis was undertaken to evaluate the non-hematological adverse events (AEs), and to explore their potential associations with survival. Results: This analysis was based on 1468 pts as of 12/21/2017. The most common non-hematological AEs were hypertension (HTN; 22.8%), proteinuria (PTN; 18.1%), fatigue (16.7%), diarrhea (11.9%) and hand-foot-skin reaction (HFSR; 9.7%), irrespective of the relationship with medication. They were not correlated with progression free survival (PFS); however, pts with diarrhea or HFSR had a statistically longer overall survival (OS) (8.41 vs. 6.14 mos, p= 0.0048; 8.31 vs. 5.98 mos, p< 0.0001) (Table). After adjusting for baseline characteristics and treatment dose, presence of HFSR was an independent predictor for prolonged OS (HR: 0.62 [95%CI, 0.44–0.88]). Besides, we assessed hepatotoxicity and cardiotoxicity in pts. 269 (18.3%) pts who developed hepatotoxicity had a statistically longer PFS (4.70 vs. 3.38 mos; p= 0.0458). A low incidence of cardiotoxicity (2.1%) was detected, and it was not related to survival. Conclusions: Occurrence of HFSR could be an effective prognostic factor for OS in apatinib-treated gastric cancer pts, whereas hepatotoxicity might predict PFS. Clinical trial information: NCT02426034.Relationship between non-hematological AEs and survival. PFS, 95%CI (mos) OS, 95%CI (mos) HTN + 3.25, 2.89–4.63 6.57, 5.49–7.59 - 4.40, 3.32–4.70 6.51, 5.72–7.29 p 0.1797 0.7761 PTN + 4.27, 3.02–4.73 7.23, 6.21–7.85 - 3.91, 3.09–4.63 6.05, 5.29–6.93 p 0.9407 0.0849 Fatigue + 4.07, 3.06–4.73 5.78, 4.93–7.23 - 4.21, 3.09–4.67 6.67, 5.98–7.69 p 0.8237 0.1813 Diarrhea + 4.70, 3.55–5.29 8.41, 7.03–9.36 - 3.71, 2.99–4.60 6.14, 5.49–6.67 p 0.0713 0.0048 HFSR + 4.70, 4.27–5.52 8.31, 6.93–12.75 - 3.55, 2.99–4.60 5.98, 5.45–6.80 p 0.1264 < 0.0001 Hepatotoxicity + 4.70, 4.21–5.78 7.23, 5.78–8.67 - 3.38, 2.96–4.47 6.08, 5.59–6.83 p 0.0458 0.1860 Cardiotoxicity + 5.52, 2.27–9.20 6.57, 4.70–9.20 - 4.01, 3.15–4.63 6.51, 5.78–7.23 p 0.3623 0.8523
PS3 KEYNOTE-024 Update: Pembrolizumab vs Platinum-Based Chemotherapy for Advanced NSCLC with PD-L1 Tumor Proportion Score ≥50%
Authors: J. Brahmer, D. Rodríguez-Abreu, A. Robinson, R. Hui, T. Csőszi, A. Fülöp, M. Gottfried, N. Peled, A. Tafreshi, S. Cuffe, M. O'Brien, S. Rao, K. Hotta, A. Riccio, J. Yang, M.C. Pietanza, M. Reck
Journal: Journal of Thoracic Oncology (2018)
KEYNOTE-051: An update on the phase 2 results of pembrolizumab (pembro) in pediatric patients (pts) with advanced melanoma or a PD-L1–positive advanced, relapsed or refractory solid tumor or lymphoma.
Authors: Birgit Geoerger, Hyoung Jin Kang, Michal Yalon-Oren, Lynley V. Marshall, Catherine Vezina, Alberto S. Pappo, Theodore Willis Laetsch, Antonio Sergio Petrilli, Martin Ebinger, Jacek Toporski, Julia Glade-Bender, Wayne Nicholls, Elizabeth Fox, Steven G. DuBois, Margaret Macy, Susan Lerner Cohn, Kumudu Pathiraja, Scott J. Diede, Scot Ebbinghaus, Navin R. Pinto
Journal: Journal of Clinical Oncology (2018)

10525 Background: In the phase 1 portion of KEYNOTE-051 (NCT02332668), the 2-mg/kg-Q3W dose of pembro was identified as the pediatric recommended phase 2 dose. We provide an update on the safety and efficacy of this dose by tumor type in the ongoing phase 2 trial. Methods: Pts aged 6 mo to < 18 y with advanced melanoma or a PD-L1–positive, advanced relapsed/refractory solid tumor or lymphoma and measurable disease per RECIST v1.1 received pembro 2 mg/kg Q3W until confirmed disease progression per irRECIST by investigator review, intolerable toxicity, or pt/investigator decision to discontinue. Key efficacy end points were ORR and PFS per RECIST v1.1 by investigator and OS (data cutoff Oct 10, 2017). Results: 689 of 748 prescreened pts had PD-L1–evaluable tumors. Of these, 229 (33.2%) were PD-L1–positive; 125 pts (median age, 13 y [range, 1-17]) were enrolled and treated (10 Hodgkin lymphoma [HL]; 115 other tumors). Median follow-up was 5.7 mo (range, 0.2-29). Primary diagnoses were other non–central nervous system (CNS) solid tumors (46%), sarcoma (19%), CNS tumors (26%), and lymphoma (9%). Seven (6%) pts experienced grade 3-5 treatment-related AEs; of these, 2 (1.6%) discontinued (1 due to increased aspartate aminotransferase; 1 with renal medullary carcinoma died of treatment-related pulmonary edema). No major untoward effects on the developing immune system were observed. One pt (10.0%) with HL achieved CR and 5 (50%) achieved PR. Six (5.2%) pts with other tumors achieved prolonged PR (2 adrenocortical carcinoma and 1 each epithelioid sarcoma, mesothelioma, malignant ganglioglioma, and lymphoepithelial carcinoma). ORR was 60.0% (95% CI, 26.2-87.8) in pts with HL and 5.2% (95% CI, 1.9-11.0) in pts with all other tumor types. Median PFS was 12.2 mo in HL and 1.9 mo in any other tumor type; 12-mo PFS was 56.3% and 8.3%, respectively. Four (40.0%) pts with HL and 19 (16.5%) with any other tumor type survived ≥12 months. Conclusions: Pembro was well tolerated and showed response in HL and in a few rare tumor types, which warrants further study. Enrollment in KEYNOTE-051 is ongoing. Clinical trial information: NCT02332668.
Trends and patterns of social media utilization at annual ASCO meetings.
Authors: Ankit J. Kansagra, Saurabh Dahiya, Shraddha Kansagra, Wilson C. Mertens, James A. Stewart
Journal: Journal of Clinical Oncology (2016)

e18021 Background: The use of social media is expanding in medicine. More and more healthcare professionals, patients and advocates are using social media as a common platform to enhance communication. Methods: Each year American Society of Clinical Oncology (ASCO) creates a hashtag (#) followed by year of the annual meeting (e.g. ASCO 2015 had this hashtag: #ASCO15) on Twitter. We conducted a retrospective study of annual meeting’s hashtag use on Twitter for past 4 annual meetings using data from Symplur, LLC. Following hashtags were used for analysis, #ASCO12, #ASCO13, #ASCO14 and #ASCO15. Results: Overall there is an increasing trend for use of annual meeting’s hashtag (see table 1). Last year’s meeting generated over 354 million impressions. Number of tweets being sent out is growing exponentially every year. More Twitter users are engaging in conversations than the year before using annual meeting’s hashtag. Last year almost 16,000 individual Twitter accounts were used during the annual meeting. Number of tweets per participant has stayed relatively constant over past four years. @asco remains the most commonly mentioned Twitter handle every year since 2012. In 2015 itself, @asco was mentioned over 7000 times. Conclusions: Twitter is a very powerful tool that amplifies the content of scientific meetings. Use of Twitter using meeting’s hashtag is increasing every year at annual ASCO meetings. This analysis provides a snapshot of Twitter activity at the conference. Avenues for further research are: trend identification,
Predictive score of early mortality in patients with solid tumors enrolled in phase I clinical trials.
Authors: Lisardo Ugidos, Valentina Boni, Elena Garralda, Maria Jose de Miguel Luken, Rafael Alvarez-Gallego, Jesus Rodriguez-Pascual, Estela Vega, Cesar Munoz, Cesar Garcia-Rey, Antonio Cubillo, Emiliano Calvo
Journal: Journal of Clinical Oncology (2017)

e14029 Background: A usual inclusion criterion for phase I trials is life expectancy of more than 3 months. Prediction of early mortality (EM), in the first 90 days after starting treatment, is thus a challenge. Predictive scores may help to select more adequate patients (pts). Our main objective was to generate a predictive score in a training set of phase I pts and to confirm it in a validation score. Secondly, we figured out if our score also predicts overall survival (OS). Methods: Consecutive pts treated in our phase I unit between 2008 and 2013 were retrospectively reviewed. We collected 35 clinical and analytical characteristics at base line. Stepwise regression was used to correlate pts characteristics with EM and generate a predictive score. Log-rank regression and Kaplan Meier curves were used to study survival. Results: We identified 438 pts. Median age was 61 yr (18-87) and 52.7% were male. More frequent tumor types were gastrointestinal (37%), thoracic (17%), and breast (12%). Pts treated with chemotherapy were 32%, targeted therapy 36%, combination 29%, and immunotherapy 3%. Response rate was 12.4%. Median progression free survival (PFS) and OS were 2.6 and 8.5 months respectively. Most common causes of discontinuation were tumor progression (87.2%) and toxicity (5.7%). EM rate was 20.5%. We randomly included 243 pts in the training score. In multivariate stepwise regression, 6 features were related to EM: ECOG PS 2 (vs 0-1), gastrointestinal or thoracic tumors (vs other types), red cell counts below 4*10 6 /ml, LDH above 600 U/L, calcium below 8.6 mg/dL, and ratio neutrophil/lymphocyte above 5. An EM score was generated ranging 0-7 (2 points for ECOG PS and 1 point for each other characteristic). Using cut off value of 0-2 vs 3 or more, we would reduce EM90 rate to half (11%) and avoid inclusion of 60% pts with EM. Our EM score was validated in the second cohort; we reduced EM rate to 10.5% avoiding undesirable inclusion of 59% pts. Applying score to all pts, median OS was 16, 8.4, 4.4, and 3 months for score 0, 1, 2, and 3-7 respectively (p &lt; 0.01). Conclusions: Our score can avoid inclusion of 60% of pts who would die before 90 days, reducing EM rate from 20 to 10%. This score can identify four prognostic groups with different median OS.
Outcomes and prognostic factors of radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) for newly diagnosed, localized extranodal NK/T-cell lymphoma, nasal type (ENKL): a cooperative study in Japan.
Authors: Motoko Yamaguchi, Ritsuro Suzuki, Masahiko Oguchi, Naoko Asano, Jun Amaki, Takeshi Maeda, Nobuko Kubota, Yukio Kobayashi, Kyoko Ueda, Kana Miyazaki, Naoto Tomita, Nodoka Sekiguchi, Jun Takizawa, Bungo Saito, Tohru Murayama, Toshihiko Ando, Hideho Wada, Rie Hyo, Masatoshi Hasegawa, Naoyuki Katayama
Journal: Journal of Clinical Oncology (2016)

7541 Background: A previous phase I/II study of RT-DeVIC for newly diagnosed, localized ENKL demonstrated promising efficacy (5y-overall survival [OS], 70%; 5y-progression-free survival [PFS], 63%; %CR, 77%) and manageable toxicity (G3 mucositis, 30%; G3 infection, 26%) (JCO 2009, 2012). RT-DeVIC has been included as a suggested treatment regimen in the NCCN guidelines since 2011. However, the outcomes in clinical practice (CP) and prognostic factors of RT-DeVIC are largely unknown. Methods: This cooperative study by hemato-oncologists and radiation oncologists in Japan (UMIN000015491) retrospectively analyzed data from patients (pts) with ENKL who were diagnosed between 2000 and 2013. Results: Data from 358 pts with ENKL of any stage were collected from 31 institutes. RT-DeVIC was the most common first-line therapy in pts with localized ENKL (168/256, 66%). The median dose of RT was 50 Gy. A two-thirds dose of DeVIC was selected in 82% of the pts. With a median follow-up of 5.1 yrs, the 5y-OS and PFS of RT-DeVIC in 168 pts were 71% and 61%, respectively. In 149 pts who were treated with RT-DeVIC in CP, 37% were age > 60 yrs, and 28% had elevated serum LDH levels. With a median follow-up of 4.9 yrs, the 5y-OS and PFS of 149 pts were 71% (95% CI, 62-78%) and 60% (95% CI, 51-68%), respectively. The %CR was 82%. There was no treatment-related death. G3/4 mucositis was recorded in 38% (G3, n = 53; G4, n = 2), and G3/4 infection occurred in 22% (G3, n = 30; G4, n = 1) of 144 evaluable pts who received RT-DeVIC in CP. These toxicities were transient and manageable. A multivariate analysis in 146 pts with localized ENKL who were treated with RT-DeVIC identified soluble interleukin-2 receptor (sIL-2R) > upper limit of normal (ULN) and ECOG PS > 1 as independent factors for worse OS. Of note, a multivariate analysis identified sIL-2R > ULN as the sole independent factor for worse PFS (HR, 3.46; P < .001). Conclusions: The efficacy and safety of RT-DeVIC was validated by the large number of pts in this study. Elevated pretreatment sIL-2R was associated with worse OS and PFS in pts with localized ENKL who received RT-DeVIC.
Tumor expression of hypoxia-inducible factor and antimicrobial peptides in oral fluid for prediction of after-surgery suppurative complications in patients with oral mucosa cancer.
Authors: Ekaterina Komarova, Oleg Ivanovich Kit, Vladimir Kononenko, Aleksey Yurievich Maksimov, Victoria V. Pozdnyakova, Inna Arnoldovna Novikova, Aleksandra Demidova
Journal: Journal of Clinical Oncology (2017)

e17530 Background: It is believed that hypoxia-inducible factor (HIF-1α) hyperactivity promotes synthesis of protective factors and increases bacterial growth-inhibitory activity, provides enhancement methods of the congenital immune response to microbial infection. Methods: Lactoferrin and α-defensin were detected in saliva of 41 patients with oral mucosa (OM) cancer (T2N0-2M0) before a comprehensive treatment; enzyme immunoassay (EIA) method was used. A level of hypoxia-inducible factor (HIF-1α) was evaluated by EIA method in tumor tissues after surgical treatment. The patients were divided into two groups according to an after-surgery period: the main group (n = 16) had after-surgery suppurative complications. An after-surgery period proceeded without infectious complications in patients of a control group (n = 25). Results: It was found that Lactoferrin content in saliva statistically was significantly higher by 36,4% (p &lt; 0,05) (3,0±0,24 µg/ml against 2,2±0,19 µg/ml) if to draw a comparison between the main group and the control group with respect to development of suppurative complications and absence of a inter-group difference according to α-defensin concentration (4,1±0,35 pg/ml against 3,8±0,19 pg/ml). HIF-1α expression index in the main group (8,4±0,79 CU/mg protein in a well) exceeded this index by 18,3% (p &lt; 0,05) in the control group (7,1±0,79 CU/mg protein). A positive correlation between HIF-1α expression and Lactoferrin content (R = 0,53 at р = 0,0001) was detected in patients with OM cancer. Conclusions: Detected HIF-1α hyperexpression in tumor tissues and Lactoferrin content in saliva, as well as their interaction allows suggesting significance of these factors for their progression prediction in patients with OM cancer in case of after-surgery suppurative complications.
Enhancing radioiodine (RAI) incorporation into BRAFV600E-mutant, RAI-refractory thyroid cancers with the BRAF inhibitor vemurafenib: A pilot study.
Authors: Lara Dunn, Eric Jeffrey Sherman, Shrujal S. Baxi, Ravinder K. Grewal, Keith S. Pentlow, Sofia Haque, R. Michael Tuttle, Mona Sabra, Stephanie Fish, Laura Boucai, Ai Ni, Jeffrey Knauf, David G. Pfister, James A. Fagin, Alan Loh Ho
Journal: Journal of Clinical Oncology (2016)

6099 Background: For patients with radioactive iodine (RAI)-refractory, recurrent/metastatic thyroid cancer, treatment entails indefinite exposure to tyrosine kinase inhibitors and their associated toxicities. The mitogen activated protein kinase (MAPK) signaling pathway is commonly activated in thyroid cancer and suppresses genes required for iodine uptake and retention, leading to RAI refractoriness. In a previous pilot study, the MEK inhibitor selumetinib restored RAI uptake; however, the response was attenuated in patients with BRAF-mutant tumors. Methods: We are conducting a study to determine whether direct targeting of BRAF activity with vemurafenib in patients with BRAF-mutant thyroid cancer reverses RAI-refractoriness. The primary objective is to determine the proportion of patients with restoration of RAI uptake sufficient to enable therapeutic RAI. Patients were stimulated with thyrotropin alfa and underwent 124I PET scans prior to and 4 weeks after treatment with vemurafenib (960mg oral twice daily). Patients whose second 124I PET scan demonstrated that > 2000 cGy could be delivered to a lesion using < 300 mCi of 131I, received therapeutic 131I while continuing vemurafenib. Results: 12 patients with BRAF-mutant thyroid cancer were enrolled; 2 were removed from study prior to the second 124I PET scan and were replaced. The median age was 68 (range 43-72) with 7 (58%) men. Vemurafenib increased 124I PET lesional dosimetry sufficient to warrant therapeutic 131I in 4 of 9 evaluable patients. Of these, 3 exhibited tumor regression (1 PR, 2 SD) at 6 months following RAI and 1 has yet to undergo follow-up imaging. Decrease in thyroglobulin levels and tumor regressions on vemurafenib prior to RAI were observed. Analysis of transcriptional signatures to assess MAPK pathway inhibition and thyroid-specific gene expression is ongoing. Conclusions: These preliminary results suggest that vemurafenib can enhance RAI incorporation and efficacy in a subset of patients with BRAF-mutant thyroid cancer. We are currently investigating whether MAPK or thyroid-specific transcriptional output markers in tumor specimens identify patients most likely to respond. Clinical trial information: NCT02145143.
Abstract 19967: Tracking Monocytes Homing to Atherosclerosis by MRI
Authors: Miao Wang, Hui Qiao, Bao Ha, Jia Zhong, Hualei Zhang, Garret A FitzGerald, Rong Zhou
Journal: Circulation (2010)

Monocyte-endothelium interaction plays a crucial role in atherogenesis. The purpose of this study is to develop a non-invasive imaging approach to track monocyte homing to the arterial wall contain...