tbuckley/cabot-search huggingface dataset:
Watson for Oncology applied to teaching and remote consulting model.
Authors: Juemin Fang, Xianling Guo, Zhongzheng Zhu, Hui Wang, Fei Hu, Jianhua Chen, Song Gao, Liting Guo, Yu Zhao, Min Yuan, Qing Xu
Journal: Journal of Clinical Oncology (2019)

6545 Background: IBM Watson for Oncology (WFO) is developed with artificial intelligence to assist the oncologists in treatment decision-making by providing evidence-based treatment recommendations with priority and personality. We have been exploring the value of applying WFO in teaching and remote consulting among members in the hospital union to improve medical quality and conformity. Methods: Four modes were followed to apply WFO to teaching and remote consulting. Firstly, a teaching hospital conducted instructional teaching for a primary hospital through WFO, or a primary hospital consulted with a teaching hospital on cancer treatment combined with WFO. Secondly, a teaching hospital conducted conference-based teaching and remote consulting for two or three primary hospitals through demonstrating WFO. Thirdly, we cooperated with other teaching hospitals to carry out interactive discussions on cases through WFO with several primary hospitals. Fourthly, we cooperated with other teaching hospitals to conduct WFO demonstration and discussion for several primary hospitals. Remote communication was performed by using third-party video conference software. A survey was conducted to collect feedback from 56 primary hospitals in our hospital union. Results: More than 80% of primary hospitals were willing to learn the standardized treatment and recent treatment progress of tumors by participating in WFO remote consulting in our hospital. The value of four modes to promote the standardized cancer treatment and improve the medical quality and conformity in primary hospitals were all recognized. WFO also contributed to academic exchanges and learning among high-level teaching hospitals, and facilitated the use of artificial intelligence in oncology therapy more rational and appropriate. Conclusions: Non-standardization in cancer care remains to be a big problem in primary hospitals in China. Although limitation of WFO exists in the complex cases of certain tumor types, the rational use of WFO in the teaching and remote consulting could help and promote the standardized cancer treatment in China.
An analysis of nivolumab-mediated adverse events and association with clinical efficacy in resected stage III or IV melanoma (CheckMate 238).
Authors: Mario Mandalà, James M.G. Larkin, Paolo Antonio Ascierto, Michele Del Vecchio, Helen Gogas, C. Lance Cowey, ANA Maria Arance Fernandez, Stéphane Dalle, Michael Schenker, Jean Jacques Grob, Vanna Chiarion-Sileni, Ivan Marquez-Rodas, Marcus Butler, Anna Maria Di Giacomo, Mark R. Middleton, Jose Lutzky, Michael Millward, Veerle de Pril, Maurice Lobo, Jeffrey S. Weber
Journal: Journal of Clinical Oncology (2019)

9584 Background: In both previous 18- and 24-month follow-up reports from CheckMate 238, NIVO demonstrated significantly longer recurrence-free survival (RFS) than ipilimumab (IPI) in patients (pts) with resected stage IIIB/C or stage IV melanoma. Here we provide a more comprehensive analysis of treatment-related adverse events (TRAEs) for NIVO over discrete follow-up intervals and an investigation of the association of these AEs with efficacy (RFS). Methods: Eligible pts were aged ≥15 years and underwent complete resection of stage IIIB/C or IV melanoma. A total of 453 pts were treated with NIVO 3 mg/kg Q2W for up to 1 year. The primary endpoint was RFS. Pts were followed for safety for up to 100 days following their last dose; as of the previous 18-month database lock, all pts had been off study drug for &gt; 100 days. Here safety data were analyzed within discrete time intervals: months 0–3 of treatment (0–3), months 3–12 of treatment (3–12), and from last dose to 100 days after last dose (+100). In addition, the association of TRAEs with RFS was investigated using the 24-month efficacy dataset, accounting for time-delay bias within the first 12 weeks after randomization. Results: The incidence of the first onset of TRAEs reported in ≥5% of pts was highest in the 0–3 time frame; the most common TRAEs with NIVO were fatigue (28% for 0–3 vs 6% for 3–12 vs 2% for +100), pruritus (16% vs 7% vs 1%), and diarrhea (15% vs 7% vs 2%). Most TRAEs with NIVO resolved within 3 months of occurrence, except for endocrine AEs, which could have required hormone supplementation, and skin AEs (median overall resolution time of 48 and 22 weeks, respectively). Similar results were observed in an analysis taking into account repeat occurrences of TRAEs over time. Analyses investigating the association of TRAEs with RFS are ongoing and will be presented. Conclusions: These results in pts with resected stage IIIB/C or IV melanoma are consistent with the established safety profile of NIVO. Based on the time periods analyzed, the majority of TRAEs with adjuvant NIVO occurred early during treatment, and patients had a reduced frequency of TRAEs after the treatment course. The majority of select TRAEs resolved within 3 months. Clinical trial information: NCT02388906.
Fulvestrant versus everolimus plus exemestane for patients with metastatic breast cancer resistant to aromatase inhibitors: Clinical experience from real world.
Authors: Yi Li, Yizhao Xie, Yannan Zhao, Xi-Chun Hu, Jian Zhang, Shen Chen, Chengcheng Gong, Sheng Zhang, Leiping Wang, Biyun Wang
Journal: Journal of Clinical Oncology (2019)

e12522 Background: To present treatment patterns and the outcome of pure endocrine therapy fulvestrant (FUL) versus Exemestane (EXE)and target therapy everolimus (EVE) combination among hormone receptor-positive (HR+)/human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (MBC) after progression on aromatase inhibitor (AI) in the real-life setting. Methods: Patients with HR+/HER2- MBC after AI who received FUL or EVE-EXE between June 2013 and June 2016 were identified from electronic database. Outcome measures included progression free survival (PFS), overall survival (OS) and safety profile. Propensity score matching (PSM) was applied to minimize potential confounders. Results: Among the 168 patients included, 124 patients received FUL and 44 patients treated with EVE-EXE. Patients that received EVE-EXE were significantly younger, more likely to have visceral, liver, multiple sites of metastases and had received more prior chemotherapy than FUL group. There was no significant difference in PFS after adjusted for propensity score between two groups (HR,1.173; 95%CI, 0.797-1.727; p = 0.419). In subgroup analysis, treatment effects were consistent across predefined subgroups except for the subgroup of multiple metastatic sites which the median PFS was significantly longer in EVE-EXE group than in FUL group (6.1vs3.2months, respectively; HR = 0.508;95%CI,0.299-0.862; p = 0.012). The toxicity of FUL regimen was more manageable. More patients discontinued the treatment due to intolerable toxicity in EVE-EXE group than FUL group. Conclusions: We observed substantial changes in treatment patterns in patients received EVE-EXE and FUL. Treatment outcomes were comparable between two schedules after adjusted for confounding factors, while FUL has been better tolerated. Clinical trial information: NCT03695341.
Efficacy and safety of pembrolizumab in patients with PD-L1 positive advanced biliary tract cancer (BTC): A prospective cohort study.
Authors: Junho Kang, Changhoon Yoo, Jae Ho Jeong, Boyeong Kang, YunJin Hong, Kyu-Pyo Kim, Baek-Yeol Ryoo
Journal: Journal of Clinical Oncology (2019)

4082 Background: For patients with advanced BTC, standard chemotherapy has limited benefit and no molecular targeted agents have been approved. Pembrolizumab is an anti PD-1 immune checkpoint inhibitor which has shown modest activity for advanced BTC patients in prior single-arm phase I/II studies. Considering the heterogeneity of BTC, more data are needed to evaluate the clinical outcomes of pembrolizumab in unresectable or metastatic BTC. Methods: In this prospective cohort study, 39 patients with PD-L1 positive BTC who received pembrolizumab in Asan Medical Center, Seoul, Korea were included (ClinicalTrials.gov identifier, NCT03695952). PD-L1 expression was assessed using immunohistochemistry and PD-L1 positive tumors were defined as the expression of PD-L1 in ≥ 1% of tumor cells. Pembrolizumab was given at a fixed dose of 200 mg intravenously, every 3 weeks. Results: The median age was 61 years old (range, 41-76) and 22 (56.4%) patients were male. Intrahepatic cholangiocarcinoma (CCA) was the most common type (n = 18, 46.2%), followed by gallbladder cancer (n = 12, 30.8%) and extrahepatic CCA (n = 9, 23.1%). Most of the patients had distant metastasis (n = 37, 94.9%). Pembrolizumab was administered as 2nd-, 3rd- and 4th or greater line chemotherapy in 18 (46.2%), 16 (41.0%) and 5 (12.8%) patients, respectively, and median 2 cycles (range 1-10) of pembrolizumab were given. In 36 patients whose response was assessable, partial response (PR) and stable disease were achieved in 4 (11.1%) and 13 (36.1%), respectively. In 19 (52.8%) patients, progressive disease was the best response. In patients with PR, the median time to response was 2.1 months (95% confidence interval (CI), 0.4 – 3.9). With a median follow-up duration of 4.4 months (95% CI, 2.4 – 6.4), median progression-free survival and overall survival was 1.5 months (95% CI, 0.4 – 2.6) and 4.3 months (95% CI, 2.6 – 6.1), respectively. No grade 3/4 adverse events (AEs) were reported and grade 1/2 fatigue (n = 4, 10.3%) was the most common AE. Conclusions: In PD-L1 positive BTC, pembrolizumab showed modest efficacy with 11.1% of response rates although our patients were heavily pretreated. Considering the limited therapeutic options and poor survival for these patients, further evaluation of immunotherapy including biomarker analysis is needed.
Case 17-2019: A 44-Year-Old Man with Joint Pain, Weight Loss, and Chest Pain
Authors: Sheila L. Arvikar, Sara R. Schoenfeld, Andrew S. Fox, Varsha K. Tanguturi, Lena D. Stuart
Journal: New England Journal of Medicine (2019)

A 44-year-old man was admitted to the hospital because of joint pain, weight loss, and chest pain. CT revealed small-volume ascites, a moderate-to-large pericardial effusion, and small bilateral pleural effusions. Echocardiography was notable for pericardial tamponade. Diagnostic tests were performed.
First experience of LOXO-292 in the management of pediatric patients with RET-altered cancers.
Authors: Ulrike Gerdemann, Young Ah Lee, Dahlia Henry, Steven Smith, Michael Vincent Ortiz, Stephen M. Rothenberg, Sandya Govinda Raju, Michael Craig Cox, Julia Lynne Glade Bender, Alberto S. Pappo, A. Lindsay Frazier, Hyoung Jin Kang
Journal: Journal of Clinical Oncology (2019)

10045 Background: Genomic alterations of RET kinase, including chromosomal fusions and activating point mutations, have been identified as oncogenic drivers in pediatric and adult cancers. Multikinase inhibitors have modest activity against RET-altered cancers and are associated with significant toxicity. LOXO-292 is a potent, ATP-competitive, small molecule RET inhibitor with high selectivity for RET, preclinical activity in the brain and excellent pharmacokinetic properties. In an ongoing phase 1/2 study of adult and adolescent patients with advanced RET-altered cancers, LOXO-292 demonstrated marked antitumor activity and was well tolerated. Methods: Pediatric patients with RET-altered cancers who were unable to access LOXO-292 through a phase 1/2 clinical trial were enrolled using FDA-allowed, IRB-approved single patient protocols . Patients received LOXO-292 (capsule/liquid formulation) orally, continuously, at a starting dose of 90 mg/m 2 BID. Response was assessed locally by investigators. Results: As of January 31, 2019, 4 female patients aged 13 months–8 years were enrolled from the Republic of Korea (papillary thyroid cancer, n = 1) and the USA (infantile myofibroma/hemangiopericytoma, n = 1; congenital mesoblastic nephroma/infantile fibrosarcoma, n = 1; lipofibromatosis, n = 1). All tumors harbored RET gene fusions (5′ partners: CCDC6, MYH10, SPECC1L, and NCOA4, respectively), detected by next-generation sequencing. Previous therapies included surgery/iodine 131 (n = 1); vandetanib (n = 1); surgery/chemotherapy (n = 1); 1 patient was treatment-naïve. Duration of treatment ranged from 3–120 days and all patients remain on treatment. There were no dose modifications or discontinuations due to adverse events. There were no treatment-related adverse events ≥ grade 3. Two patients who were evaluable for response had partial responses (both ongoing, 1 confirmed, 1 pending confirmation). Conclusions: These preliminary data from a real-world setting suggest that LOXO-292 is effective and safe in pediatric patients whose tumors harbor RET gene fusions.
A Nationwide analysis of mortality trends in geriatric and non-geriatric patients with oral cavity tumors.
Authors: Bushra Waseem, Germame Hailegiorgis Ajebo, Allan N. Krutchik, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2019)

e17510 Background: Squamous cell carcinoma is the most common histological-subtype of oral cavity tumors and no major advances in its treatment have occurred recently. However, p16 positive tumors have been noted to have a better prognosis than p16 negative tumors. Older patients have increasingly been found to have p16 positive oral cavity cancers. This study explores the incidence based mortality of geriatric patients irrespective of p16 status. Methods: Data from Surveillance, Epidemiology, and End Results (SEER) Database was extracted to study the incidence-based mortality for the years 2000 to 2014. Incidence-based mortality for all stages of oral cavity tumors was queried and the results were grouped by age (geriatric vs. non-geriatric) and race (Caucasian/White, African American/Black, American Indian/Alaskan native and Asian/Pacific Islander). All stages and both genders were included in the analysis. T-test was used to determine statistically significant difference between various subgroups. Linear trend lines were used to visualize the mortality trends between various subgroups (Geriatric vs. Non- geriatric and Caucasian vs. African American). Results: Incidence-based mortality for oral cavity tumors has worsened since 2000 to 2014 for geriatric patients (p &lt; 0.05) when compared to non-geriatric patients in both Caucasian/White patients and African American/Black patients. The results are summarized in the table below. Conclusions: The similarity in incidence-based mortality for geriatric patients with oral cavity tumors is high in all races and may imply age as a significant risk factor in these patients. A stage-specific, gender-specific and age-binned analysis may help differentiate these concerning trends. [Table: see text]
Abstract 12654: Impact of a Comprehensive ST-Elevation Myocardial Infarction (STEMI) Protocol on Patients With STEMI and Cardiac Arrest
Authors: Anirudh Kumar, Chetan P Huded, Michael J Johnson, Venu Menon, Stephen G Ellis, Samir R Kapadia, Umesh N Khot
Journal: Circulation (2018)

Background: Cardiac arrest (CA) complicating ST-elevation myocardial infarction (STEMI) is associated with substantial morbidity and mortality. It is unknown whether STEMI systems can improve the c...
A phase Ib dose-escalation and cohort-expansion study of safety and activity of the transforming growth factor (TGF) β receptor I kinase inhibitor galunisertib plus the anti-PD-L1 antibody durvalumab in metastatic pancreatic cancer.
Authors: Davide Melisi, Antoine Hollebecque, Do-Youn Oh, Emiliano Calvo, Anna M. Varghese, Erkut Hasan Borazanci, Teresa Macarulla Mercade, Francesca Simionato, Joon Oh Park, Johanna C. Bendell, Sandrine J. Faivre, Yumin Zhao, Ivelina Gueorguieva, Michael Man, Shawn Estrem, Karim Adnane Benhadji, Mark Lanasa, Susan C. Guba, Rocio Garcia-Carbonero
Journal: Journal of Clinical Oncology (2019)

4124 Background: Pancreatic cancer (PC) is characterized by a highly immunosuppressive microenvironment, and immune checkpoint inhibitors as monotherapy have been ineffective to date. TGFβ is commonly viewed as a powerful immunosuppressive cytokine, and inhibition of its signaling reverses this suppression and activates adaptive immune responses. A combination of TGFβ and PD-L1 inhibition may act synergistically to induce immune restoration and to improve antitumor responses. This Phase 1b study (NCT02734160) evaluated the combination of galunisertib plus durvalumab in recurrent or refractory metastatic PC. Methods: Eligible patients (pts) were ≥18 years old, had ECOG status ≤1, and had not received treatment with anti-PD-1, anti-PD-L1, or TGFβ R1 kinase inhibitors. The primary objective was to assess the safety and the recommended dose of galunisertib given 14 days on/14 days off in combination with durvalumab 1500 mg every 4 weeks. Four dose levels of galunisertib were tested in the dose escalation portion of the study: 50 mg QD, 50 mg BID, 80 mg BID and 150 mg BID, followed by the cohort expansion portion of the study at the recommended Phase 2 dose (RP2D). Secondary objectives included preliminary assessment of activity by response rate, (RECIST v1.1), median PFS (mPFS), and OS (mOS). Results: 42 pts (25F/17M) were treated in the study (median age 56.5 y; 71.4% had received ≥2 prior systemic regimens). There was no dose limiting toxicity and galunisertib 150 mg BID was chosen as the RP2D. In the 32 pts treated at this dose, Grade ≥3 related AEs included AST and GGT elevations (2 pts each), and ALT and alkaline phosphatase elevations, and neutropenia (1 pt each). One partial response and 7/32 stable diseases were observed (disease control rate 25%); mPFS was 1.9 months (95% CI: 1.5, 2.2) and mOS was NR (95% CI: 3.6, NR). Biomarker data will be presented at the meeting. Conclusions: The combination of galunisertib plus durvalumab had an acceptable tolerability and safety profile. The activity of this combination in second and third line PC patients warrants further consideration. Clinical trial information: NCT02734160.
Retrospective single-center outcome analysis of neoadjuvant and palliative treatment with dual trastuzumab and pertuzumab in HER2-positive breast cancer.
Authors: Maximilian Marhold, Lea Roxana Ionce, Alexandra Christ, Marie-Bernadette Aretin, Verena Sagaster, Ruth Exner, Kerstin Wimmer, Yelena Devyatko, Florian Fitzal, Guenther G. Steger
Journal: Journal of Clinical Oncology (2019)

e12114 Background: Her2-positive (Her2pos) breast cancer (BCa) is the second most lethal subtype of BCa. The treatment of Her2-positive BCa was revolutionized due to the dual use of trastuzumab and pertuzumab (T+P) in recent years both in the neoadjuvant and the palliative setting. Although several years have passed after initial approval of these drugs, single-center outcome data as reported by clinicians is sparse. In this retrospective study, we set to assess outcomes measures at our institution, Austria’s largest academic hospital, for the use of T+P in early and metastasized BCa. Methods: We acquired records on combined pertuzumab and trastuzumab orders from our intramural drug order software (CATO, Cato Research, Durham, NC, USA) for the time period of May 2013 to March 2018. Further, using electronic patient histories, we described both the neoadjuvant and palliative patient groups by assessment of body weight/size, tumor stage, histology including immunohistochemistry (IHC), lines of oncological therapies received, ejection fraction (EF) drops&gt;10%, deaths and most importantly the outcomes measures pathological complete response (pCR, neoadjuvant cohort) rate and progression-free survival (PFS, palliative cohort). Results: 120 breast cancer patients were given dual therapy with T+P. The neoadjuvant cohort contained 63 patients, while the palliative cohort included 57 patients. All patients included were female. Full histology including IHC data was available for 47 of 63 patients in the neoadjuvant cohort and 30 of 57 patients in the palliative cohort. BMI was 25.6 and 23.3, respectively, on average. The mean age was 54 years in the neoadjuvant and 56 years in the palliative cohort. 73.6% (39/53) and 65.9% (29/44) of tumors were ER positive as determined by IHC. While neoadjuvant patients obtained an average of 6.5 cycles, patients within the palliative cohort received a mean of 17.3 cycles of T+P. 0 and 17 deaths were observed in the respective cohorts. Data on pCR and PFS was available for 95.2% and 91.2% of patients, respectively. The pCR rate within the neoadjuvant cohort was 46.7% (28/60), and mean PFS across all treatment lines of the palliative cohort was 10.2 months. Conclusions: We report retrospective single-center outcome data for the combined use of trastuzumab and pertuzumab in both early and metastatic Her2pos BCa in line with previously published data.
WhoGEM: an admixture-based prediction machine accurately predicts quantitative functional traits in plants
Authors: Laurent Gentzbittel, Cécile Ben, Mélanie Mazurier, Min-Gyoung Shin, Todd Lorenz, Martina Rickauer, Paul Marjoram, Sergey V. Nuzhdin, Tatiana V. Tatarinova
Journal: Genome biology (2019)

The explosive growth of genomic data provides an opportunity to make increased use of sequence variations for phenotype prediction. We have developed a prediction machine for quantitative phenotypes (WhoGEM) that overcomes some of the bottlenecks limiting the current methods. We demonstrated its performance by predicting quantitative disease resistance and quantitative functional traits in the wild model plant species, Medicago truncatula, using geographical locations as covariates for admixture analysis. The method's prediction reliability equals or outperforms all existing algorithms for quantitative phenotype prediction. WhoGEM analysis produces evidence that variation in genome admixture proportions explains most of the phenotypic variation for quantitative phenotypes.
Assembling the brain trust: the multidisciplinary imperative in neuro-oncology
Authors: Ethan B. Ludmir, Anita Mahajan, Verity Ahern, Thankamma Ajithkumar, Claire Alapetite, Valérie Bernier-Chastagner, Ranjit S. Bindra, Andrew J. Bishop, Stephanie Bolle, Paul D. Brown, Christian Carrie, Anthony J. Chalmers, Eric L. Chang, Caroline Chung, Karin Dieckmann, Natia Esiashvili, Lorenza Gandola, Amol J. Ghia, Vinai Gondi, David R. Grosshans, Semi B. Harrabi, Gail Horan, Danny J. Indelicato, Rakesh Jalali, Geert O. Janssens, Mechthild Krause, Nadia N. Laack, Normand Laperriere, Anne Laprie, Jing Li, Karen J. Marcus, Susan L. McGovern, Thomas E. Merchant, Kenneth W. Merrell, Laetitia Padovani, Jeannette Parkes, Arnold C. Paulino, Rudolf Schwarz, Helen A. Shih, Luis Souhami, Erik P. Sulman, Roger E. Taylor, Nicola Thorp, Beate Timmermann, Greg Wheeler, Suzanne L. Wolden, Kristina D. Woodhouse, Debra N. Yeboa, Torunn I. Yock, Rolf-Dieter Kortmann, Mary Frances McAleer
Journal: Nature Reviews Clinical Oncology (2019)