tbuckley/cabot-search huggingface dataset:
What predicts minimal response to abiraterone in metastatic castrate resistant prostate cancer?
Authors: Rhian Sian Davies, Christian Smith, Ricky Dylan Frazer, Mick Button, Jacob Tanguay, Jim Barber, Nachi Palaniappan, John Staffurth, Jason Francis Lester
Journal: Journal of Clinical Oncology (2015)

e16103 Background: There are several treatments that have been shown to prolong survival in metastatic castrate resistant prostate cancer (mCRPC), and the optimum sequencing of these has not yet been established. Personalised medicine is using genetic predictors to tailor treatment to the individual, which avoids using expensive potentially toxic therapy in patients who have minimal chance of benefit. The use of genetic predictors in mCRPC is some way off routine clinical practice. There is an urgent need for a practical method of identifying patients who are unlikely to respond to a particular treatment so that a more appropriate therapy can be used. We have performed a detailed analysis of patients with mCRPC receiving multiple lines of therapy to identify a cohort who will have limited benefit from abiraterone. Methods: A retrospective analysis of 47 consecutive patients with mCRPC treated in a single cancer centre was conducted. Patients were treated sequentially with androgen deprivation (Lutenising Hormone Releasing Hormone agonist/LHRHa or orchidectomy), bicalutamide, docetaxel plus prednisolone, followed by abiraterone. Data were collected on patient and disease demographics, treatment received and response. Progression was defined as clinical, radiological or PSA relapse. Results: Median age was 74 years (range 55-84). Median progression-free survival and overall survival from commencement of abiraterone in responders versus non-responders of each line of treatment was compared using Log Rank analysis. The results are displayed in Table. Conclusions: ≤ 18 months to progression on LHRHa, no response to bicalutamide and ≤ 6 months response to docetaxel were strong predictors of significantly shorter progression-free and overall survival from commencement of abiraterone. N Median PFS (days) Log Rank Median OS (days) Log Rank LHRHa response ≤18 months 29 118 P = 0.018 348 P = 0.016 LHRHa response >18 months 18 279 815 Bicalutamide non-responders 16 91 P = 0.003 413 P = 0.009 Bicalutamide responders 27 196 752 Docetaxel ≤ 6 months response 20 102 P = 0.000 325 P = 0.04 Docetaxel > 6 months response 25 294 727
Trends in checkpoint inhibitor therapy for advanced urothelial cell carcinoma (aUC) at the end of life: Insights from real-world practice.
Authors: Ravi Bharat Parikh, Matt D. Galsky, Bishal Gyawali, Fauzia Riaz, Tara Laura Kaufmann, Aaron Benjamin Cohen, Blythe J.S. Adamson, Cary Philip Gross, Neal J. Meropol, Ronac Mamtani
Journal: Journal of Clinical Oncology (2019)

395 Background: National guidelines recommend against chemotherapy use at the end of life. Five CPIs are now approved for aUC. We hypothesized that oncologists may have a lower threshold to initiate CPI in patients (pts) at the end of life, particularly among pts with poor performance status (PS), because of the perceived favorable toxicity profile of CPI. Methods: We conducted a secular trend analysis using the Flatiron Health Database, a large real-world electronic medical record-derived dataset. We used nonparametric tests of trend (p values reported as p trend ) to evaluate quarterly proportions of pts initiating CPI, chemotherapy, or no systemic therapy within 30 and 60 days of death, among 2959 pts diagnosed with aUC from 2015 to 2017. Results: 1637 pts died during follow-up and were eligible for analysis. 278 (17.0%) and 488 (29.8%) pts initiated a new line of systemic therapy in the last 30 and 60 days of life, respectively. The quarterly proportion of CPI initiators within 60 days of death increased from 1.0% to 23% during the study period ( p trend &lt; 0.001), with corresponding decreases in chemotherapy initiation and no systemic therapy. After CPI approval in mid-2016, CPI initiation significantly increased among pts with Eastern Cooperative Oncology Group (ECOG) PS ≥ 2 ( p trend = 0.02) but did not significantly change among pts with PS 0-1. Initiation of any systemic therapy at the end of life doubled (17.4% to 34.8%) over the study period, driven largely by end-of-life CPI use. Compared to chemotherapy initiators, CPI initiators had slightly worse PS (table). Conclusions: In patients with aUC, there has been a dramatic rise in CPI initiation at the end of life particularly among pts with poor PS. Existing guidelines on systemic therapy initiation near the end of life should account for the increasing use of CPI. [Table: see text]
Abstract 20987: Pulmonary Blood Volume Evaluated by Dual-Energy CT is a New Maker for the Management of Chronic Thromboembolic Pulmonary Hypertension
Authors: Hiroyuki Onishi, Kazuhiko Nakayama, Ken-ichi Yanaka, Naoki Tamada, Yuto Shinkura, Yasunori Tuboi, Shinsuke Shimoyama, Tatsuya Nishii, Atushi Kono, Noriyuki Negi, Shumpei Mori, Hiromasa Otake, Seimi Satomi-Kobayashi, Toshiro Shinke, Noriaki Emoto, Ken-ichi Hirata
Journal: Circulation (2017)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary obstructive vascular disease. But there were few methods to quantify lung blood perfusion. In dual-energy CT (DECT), two image datasets are acquired in the same anatomic location using two different tube potentials. DECT can produce a more sensitive iodine distribution map image than conventional CT, which enable us to quantify blood perfusion in lung fields. There were few reports showing the clinical significance of DECT in CTEPH. Methods: We enrolled 59 consecutive CTEPH patients who underwent DECT from Jan. 2015 to Feb. 2017. We evaluated the relations between DECT parameter as lung pulmonary blood volume (PBV) and clinical parameters from 6-min walk distance (6MWD), respiratory function test, cardiopulmonary exercise test (CPX), and right heart catheterization (RHC). Results: In 59 patients (female 41, mean age 60.0±13.6 years old), two patients were WHO functional class (WHO-Fc) IV, 28 were WHO-Fc III, 23 were WHO-Fc II, six were WHO-Fc I. 28 patients were evaluated at pre-treatment, nine at post pulmonary endarterectomy (PEA), 18 at post balloon pulmonary angioplasty (BPA), and four at post hybrid therapy (PEA and BPA). The average of PBV were 25.4±7.4 Hounsfield Unit. Mean pulmonary arterial pressure (mPAP) were 29.5±12.9 mmHg, pulmonary vascular resistance (PVR) were 553±404 dyne*sec/cm5, cardiac index were 2.3±0.7 l/min/m2. The value of PBV was well reflected with WHO-Fc classification. (I/II/III/IV=31.8±6.4/27.1±7.4/22.8±6.2/23.5±13.4; ANOVA p=0.019), and was significantly correlated with mPAP (r = -0.57, p &lt; 0.01), PVR (r = -0.60, p &lt; 0.01), VE/VCO2 slope (r =- 0.47, p &lt; 0.01), BNP level (r = -0.60, p &lt; 0.01). Conclusion: PBV was positively correlated with symptom, hemodynamics, exercise capacity, and BNP level in the patients of CTEPH, suggesting that PBV by DCET can work as a new management index from a perspective of pulmonary blood perfusion.
Combination anti-angiogenic tyrosine kinase inhibition and anti-PD1 immunotherapy in metastatic renal cell carcinoma: A retrospective analysis of safety, tolerance, and clinical outcomes.
Authors: Andrew L. Laccetti, Minas P. Economides, Aradhana M. Venkatesan, Jianjun Gao, Eric Jonasch, Paul Gettys Corn, Amado J. Zurita, Nizar M. Tannir, Pavlos Msaouel, Amishi Yogesh Shah, Matthew T Campbell
Journal: Journal of Clinical Oncology (2019)

630 Background: Emerging phase III data support combination antiangiogenic tyrosine kinase inhibitors (TKIs) and immunotherapy (IO) as front line treatment for metastatic renal cell carcinoma (mRCC). Little is known about off-protocol experience and later line treatment with this therapeutic approach including tolerance, response and survival. Methods: We conducted a retrospective analysis of mRCC patients (pts) who received combination TKI-IO between 11/2015 and 05/2018 at MD Anderson Cancer Center. Chart review detailed baseline characteristics, TKI-IO treatment, toxicity and survival. An independent radiologist, blinded to pts history and clinical data, assessed radiographic response using RECIST v1.1. Results: 36 mRCC pts were identified for study inclusion: median (med) age 63.5 years, 72% clear cell histology, 53% intermediate risk (19% good, 28% poor) by IMDC, med metastatic sites 2, med prior therapies 2, previous TKI 94% and previous IO 47%. Combinations included nivolumab (nivo)-cabozantinib (15), nivo-low dose pazopanib(ldP) (13), nivo-axitinib (5), nivo-lenvatinib (2) and pembrolizumab-axitinib (1). Median time on TKI-IO was 5.6 months (m) (95% CI: 5.2 - 7.7). 56% of pts initiated TKI prior to IO addition at progression and 36% of pts initiated IO prior to TKI addition. ORR was 35% (29% PR and 6% CR); disease control rate was 78% (43% stable disease). With med follow-up of 8.0 m (95% CI: 6.4 – 9.4), med PFS was 7.7 m (95%CI: 5.8 - 9.5), med OS was not reached. Med PFS for pts receiving nivo-ldP was not reached. TKI-IO therapy was well tolerated with only 1 pt demonstrating grade 3 or 4 immune related toxicity (nephritis). 92% of pts experienced any grade of adverse events (ADE) with ADE of interest as follows: diarrhea (25%), hypothyroidism (17%), and pneumonitis (8%). Conclusions: To our knowledge, this is the first case series of off-label combinations of TKI-IO for mRCC. TKI-IO, particularly nivo-ldP, is safe, well tolerated and efficacious. Although further prospective research is essential, TKI-IO could be considered for select mRCC patients, particularly in the setting of TKI or IO refractory disease.
Efficacy of mitomycin C plus a fluoropyrimidine in pretreated patients with metastatic colorectal cancer eligible to regorafenib: Results of a retrospective study.
Authors: Federica Martorana, Stefano Sergio Cordio, Roberto Bordonaro, Paolo Giovanni Vigneri, Giuseppe Novello, Marco M Aiello, Concetta Martines, Hector J. Soto Parra
Journal: Journal of Clinical Oncology (2015)

e14661 Background: Mitomycin C (MMC) and a Fluoropyrimidines (FPDs) represent a viable treatment option for patients (pts) that would currently be eligible for Regorafenib (RGR) after the publication of the CORRECT study. This placebo-controlled trial showed a significant benefit in both median overall (OS 6.4 mos) and progression-free (PFS 1.9 mos) survival for pts with metastatic colo-rectal cancer (mCRC) receiving RGR. All subjects displayed PS 0-1 according to the ECOG scale and had previously failed all standard therapies which must have included FPDs, Oxaliplatin, Irinotecan, Bevacizumab, and Cetuximab or Panitumumab (for K-RAS WT pts). Methods: We retrospectively evaluated the clinical records of mCRC pts treated with MMC+FPDs that fulfilled inclusion/exclusion criteria of CORRECT study to evaluate their OS and PFS. Results: Records from 87 pts were collected in two Sicilian centers with 61 pts fulfilling the inclusion criteria for this analysis. Pts characteristics were: Male/Female: 38/23; median age: 69.3 (range 37-80); ECOG PS0/1: 45/16; primary site of disease: colon/rectum/colon and rectum 41/19/1; K-RAS status: WT/mutated/unknown 37/22/2; number of previous systemic anticancer therapies: 1-2/3/ ≥ 4 32/20/9; previous anti-VEGF treatment: Bevacizumab/Aflibercept and Bevacizumab 42/5; previous Cetuximab or Panitumumab or both 34/1/2. Median OS was 9.3 month (95% C.I. 9.0 to 15.4); median PFS was 3.3 month (95% CI 2.9-3.8). Partial remission, stable disease and disease control were achieved in 5%, 24.5% and 29.5% of pts respectively. No significant differences in OS and PFS were found between K-RAS WT and K-RAS mutant individuals. Likewise, PS and the primary site of disease were not associated with response differences. Conclusions: These results may suggest the need for a prospective study assessing RGR cost-effectiveness compared to MMC+FPDs in mCRC pts progressed after all standard lines of treatment.
Precision exercise medicine: understanding exercise response variability
Authors: Robert Ross, Bret H Goodpaster, Lauren G Koch, Mark A Sarzynski, Wendy M Kohrt, Neil M Johannsen, James S Skinner, Alex Castro, Brian A Irving, Robert C Noland, Lauren M Sparks, Guillaume Spielmann, Andrew G Day, Werner Pitsch, William G Hopkins, Claude Bouchard
Journal: British Journal of Sports Medicine (2019)

There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability. In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels—a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.
Health-related quality of life (HRQoL) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in combination with abiraterone.
Authors: Noel W. Clarke, Antoine Thiery-Vuillemin, Pawel J. Wiechno, Boris Alekseev, Nuria Sala, Robert Jones, Ivo Kocak, Vincenzo Emanuele Chiuri, Jacek Jassem, Aude Flechon, Charles Redfern, Carsten Dietrich Goessl, Joseph Burgents, Christopher Gresty, Arnold Degboe, Fred Saad
Journal: Journal of Clinical Oncology (2019)

234 Background: A Phase II trial showed that addition of olaparib (O) to abiraterone (A) led to significant radiographic progression-free survival benefit for patients (pts) with mCRPC vs placebo (P) + A (hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.44–0.97). We report predefined exploratory HRQoL analyses. Methods: This randomized, double-blind trial enrolled pts with mCRPC, post-docetaxel. Pts were randomized (71 per arm) to receive either O (300 mg bd, tablets) + A (1000 mg od) or P + A; all received prednisone (5 mg bd). Pts completed Functional Assessment of Cancer Therapy-Prostate (FACT-P total score [TS]; range 0–156, higher score = better HRQoL), Brief Pain Inventory–Short Form (BPI-SF) and worst bone pain (wbp) questionnaires (both range 0–10, higher score = more severe pain). Adjusted mean change from baseline was analysed using a mixed model for repeated measures, improvement by logistic regression and deterioration by log-rank test. Results: Overall compliance rates (O + A vs P + A) were 97% vs 96%, 92% vs 85%, and 96% vs 92% for FACT-P, BPI-SF and wbp, respectively. Best FACT-P TS response of ‘improved’ (increase ≥6 points from baseline at two consecutive visits) was reported by 22/67 (33%) evaluable pts in the O + A vs 18/64 (28%) pts in the P + A arm; the odds ratio (1.32; 95% CI 0.64–2.78) favored the O + A arm. Best FACT-P TS response of ‘worsened’ (decrease ≥6 points from baseline) was reported by 15 (22%) vs 22 (34%) pts. Adjusted mean change from baseline in FACT-P TS across all visits was -0.60 vs -2.09 in the O + A and P + A arms, respectively (difference 1.48; 95% CI -3.96–6.92). Time to deterioration (TTD) results are shown in the table. Clinical trial information: NCT01972217. Conclusions: Whilst not statistically significant, in this study a higher percentage of pts treated with O + A vs P + A had improved HRQoL, with fewer pts negatively affected. Ongoing phase III studies will help elucidate the impact of O on HRQoL in pts with mCRPC. (NCT01972217)[Table: see text]
Incidence of lymphonodal metastases in thyroid microcarcinomas.
Authors: Merima Oruci, Ivan Markovic, Nada Santrac, Igor Djurisic, Marko Buta, Gordana Pupic, Dusica Gavrilovic, Radan Dzodic
Journal: Journal of Clinical Oncology (2015)

e17032 Background: The aim of this study was to determine frequency of lymphonodal metastases in jugulo-carotid chain (JCC) and central neck compartment in incidental thyroid microcarcinomas (ITMC), as well as to examine whether sentinel lymph node (SLN) biopsy of JCC is an accurate technique to select patients with true positive, but clinically and ultrasonically negative lymph nodes, for modified radical neck dissection (MRND). Methods: Out of all patients operated in our Institution from 2004 to 2013 for multinodal goiter, Hashimoto's thyroiditis, adenomas, Graves' disease or increase of serum calcitonin concentration, for the purpose of this study, we have selected 117 who had ITMC and were surgically treated with total thyroidectomy (lobectomy in only one patient), sampling or complete dissection of central lymph nodes and SLN biopsy in JCC. As a standard procedure, SLN mapping was performed with 0.2ml of 1% methylene blue dye injected just beneath thyroid gland capsule. SLNs were examined by frozen section and if positive, additional MRND was done. Hystopathological analysis showed 108 papillary, 6 medullary, and 3 combined papillary and medullary thyroid microcarcinomas less than 1 cm in diameter. Results: Multicentric carcinomas were recorded in 39.32% of patients. In patients with lymphonodal metastases (24.79%), JCC metastases were found in 7.69%, central in 20.51%. Specificity and sensitivity of method are 100% and 57.14%, positive and negative predictive values are 100% and 97.3%. Method’s accuracy is 97.39%. Conclusions: Data showed high percentage of metastases in central neck compartment. SLN biopsy is a method more precise than clinical examination and ultrasonography in detection of ITMC lateral lymphonodal metastases in N0 patients. Using SLN biopsy for intraoperative assessment of lateral compartment one can avoid unnecessary MRND, as well as prevent under-treatment of patients with good prognosis. In addition, this method helps optimizing ablative radioiodine treatment.
5-Fluorotroxacitabine Displays Potent Anti-Leukemic Effects and Circumvents Resistance to Ara-C
Authors: Aniket Bankar, Thirushi Piyumika Siriwardena, Biljana Rizoska, Christina Rydergård, Helen Kylefjord, Vilma Rraklli, Anders Eneroth, Pedro Pinho, Stefan Norin, Johan Bylund, Sara Moses, Richard Bethell, Simon Kavanagh, Xiaoming Wang, Rose Hurren, Mark D. Minden, Paul Targett-Adams, Aaron D Schimmer, Mark Albertella
Journal: Blood (2018)
Serum human epididymis protein 4 (HE4) levels in colorectal cancer patients.
Authors: Yasemin Kemal, Guzin Gonullu, Addulkerim Bedir, Leman Tomak, Murat Derebey, Dilek Erdem, Ufuk Gor, Idris Yucel
Journal: Journal of Clinical Oncology (2015)

e14650 Background: Tumour markers are widely used for diagnosis, staging, and monitoring colorectal cancer (CRC) patients in clinical practice. Carcino-embryonic antigen (CEA) and carbonhydrate antigen 19-9 (CA19-9) are the most frequently used biomarkers in CRC patients. Many studies have recently investigated the presence of overexpressed HE4 (humanepididymis protein 4) in some cancer types. Its significance in ovarian and endometrial cancer is well demonstrated. Our study aimed to evaluate the importance of serum HE4 levels colorectal cancer patients. Methods: 46 newly-diagnosed colorectal carcinoma patients and 36 age and sex-matched healthy subjects were included in the study. All participants gave written informed consent. Enzyme-linked immunosorbent assay (ELISA) kit (Cusabio Biotech Co., LTD., P.R.China) was used for HE4 evaluation The concentrations of CEA and CA19.9 were also compared to HE4 levels. Results: HE4 positivity was determined in 13 of 46 cases (28.3%) in the colorectal cancer group but no HE4 positive subjects were determined in the control group (0%)(p˂0.01)(Table-1). The area under the receiver operating characteristic curve (ROC-AUC) for HE4 positivity was 0.641 (95% CI 0.523-0.760). HE4 was statistically significantly positive in patients with stage III-IV and in patients with high CA 19.9 levels (all p<0.01)(Table-2). Conclusions: This first report that examined HE4 in CRC population revealed that it could be a useful biomarker especially in stage III and IV patients. Characteristics of patients and controls. Patients (n=46) Mean ± SD Controls (n=36) Mean ± SD P value Age, year 60.5 ± 11.8 58 ± 12.5 >0.05 Frequency (%) Frequency (%) Gender Female Male 16 (34.8) 30 (65.2) 13 (36.1) 23 (63.9) >0.05 HE4 Positive 13 (28.3) 0 (0.0) <0.01 Negative 33 (71.7) 36 (100.0) Comparison of the HE4 positive and negative patients. HE4 (+) Frequency (%) HE4 (-) Frequency (%) P value Grade I II III 2 (16.7) 8 (66.6) 2 (16.7) 11 (44.0) 13 (52.0) 1 (4.0) > 0.05 Lymph node positive Lymph node negative 13 (100.0) 0 (0.0) 20 (60.6) 13 (39.4) < 0.01 Stage I-II Stage III-IV 0 (0.0) 13 (100.0) 13 (39.4) 20 (60.6) < 0.01 CEA ≥ 3.7 CEA <3.7 11 (84.6) 2 (15.4) 17 (58.6) 12 (41.4) > 0.05 CA 19.9≥37 CA 19.9<37 11 (84.6) 2 (15.4) 6 (20.7) 23 (79.3) <0.001
Novel algorithms to predict the occurrence of in-hospital venous thromboembolism in cancer patients: Machine learning classifiers developed from the 2012 national inpatient sample.
Authors: Spencer L. James, Kabir Mody, Joseph James Shatzel
Journal: Journal of Clinical Oncology (2015)

1582 Background: Cancer poses a significant risk for venous thromboembolism (VTE), but predicting VTE in patients is challenging. Oncology admissions accrue significant amounts of clinical data, but currently only a limited amount of this data is used to predict VTE. Machine learning is a discipline of computer science whereby computers study high dimensional data features to discover rules that can predict an outcome. The advent of the electronic medical record (EMR) offers a plethora of patient-specific data that could be used for more complex risk modeling, although it is unknown whether this can accurately be used to predict VTE occurrence in the oncology patients. We aimed to measure the accuracy of machine learning classifiers in predicting VTE in patients hospitalized with cancer using information that would be available to the EMR. Methods: Using the 2012 National Inpatient Sample (NIS), we applied multiple different machine learning classifiers to develop a predictive model of cancer associated in-hospital VTE and tested its ability to predict which cancer related admissions would be associated with VTE. Accuracy was measured as the percentage of admissions correctly associated with VTE. Results: Of the 7,296,968 admissions in the 2012 NIS, 996,506 were associated with a cancer diagnosis, and of those, 47,045 were associated with VTE. Of the patients with a cancer diagnosis, we sampled 1,089 with VTE and 1,089 without VTE. We then conducted 100 train-test simulations where classifiers were trained on a random sample of the data and then made VTE predictions on a separate sample. Of the 100 trials performed, the random forest classifier in the scikit-learn package was able to correctly classify VTE versus non-VTE 74% of the time (range: 69.0% - 79.0%). Conclusions: Machine learning classification is capable of harnessing complex signals in clinical datasets and is a promising approach to assess the in-hospital VTE risk of admitted cancer patients. With further validation, such classifiers could be included in EMR systems to provide risk assessment for patient admissions and suggest appropriate use of pharmacological prophylaxis.