tbuckley/cabot-search huggingface dataset:
Technical and clinical validation of somatic CNV detection from circulating tumor DNA.
Authors: Kaican Cai, Zisong Zhou, Di Lu, Kejun Nan, Xiaochen Zhao, Yuejun Chen, Dadong Zhang, Hua Dong, Fu-Gen Li, Yu Yao
Journal: Journal of Clinical Oncology (2018)

e21055 Background: While methods for detecting SNV and indel in circulating tumor DNA (ctDNA) with hybrid-capture based next generation sequencing (NGS) has been available, algorithm for calling copy number variation(CNV) is more challenging. Here we present a method enabling CNV detection in very low amount of ctDNA with high sensitivity and specificity. Methods: First of all, we built a background model with a customized 150 gene panel cfDNA sequencing data from 10 healthy people. This model was then applied to normalize read depth to further reduce background noise. The probe level log2ratio was segmented using circular binary segmentation. Segments with log2ratio above 3 fold standard deviation was treated as amplification. Then we used NCI-H1573 and HCC1954 cell culture supernatant, which harbored three CNVs: ERBB2 (HCC1954), EGFR and MET (NCI-H1573), to mimic human ctDNA. Both in-silicon and in-vitro simulations were performed to define the detection limit. We validated the CNV concordance of FFPE samples and matched controls with WES profiling and plasma samples with 150 gene panel profiling from 28 lung cancer patients. Additional 1495 ctDNA samples were also profiled with 150 gene panel. Results: For in-silicon spike-in, the detection limit of ctDNA fraction is about 0.3% for ERBB2 (2.2 copy), 5% for MET (2.5 copy), 1% for EGFR (2.2 copy). For in-vitro spike-in, the detection limit of ctDNA fraction is about 1% for ERBB2 (2.6 copy), 5% for MET (2.5 copy), 3% for EGFR (2.6 copy). Compared with WES CNV results, the specificity of CNV calling from ctDNA panel is 95.5% and sensitivity is 50% when copy number > 6, and 71.4% when copy number > 12. We profiled 1495 lung cancer ctDNA samples with 150 gene panel and detected 15 HER2 amplification(1%), 75 EGFR amplification(5%) and 30 MET amplification samples(2%). An advanced lung adenocarcinoma patient with acquired resistance after EGFR TKI treatment, MET amplification was detected in plasma ctDNA. Patient accepted crizotinib and reached partial response. Conclusions: We developed a pipeline to detect CNV in very low amount of ctDNA with high sensitivity and specificity, which improves the accuracy of CNV calling in noninvasive way and avoids unnecessary biopsy on tumor patients.
Autologous genetically engineered NY-ESO-1<sup>c259</sup>T in HLA-A*02:01, HLA*02:05 and HLA*02:06 positive patients with NY-ESO-1 expressing tumors.
Authors: Crystal Mackall, Sandra P. D'Angelo, Stephan A. Grupp, Kunle Odunsi, Mihaela C. Cristea, Gerald P. Linette, Harriet M. Kluger, Gabor Kari, Lini Pandite, Tom Holdich, Elliot Norry, Gwendolyn Binder-Scholl, Rafael G. Amado
Journal: Journal of Clinical Oncology (2016)

TPS3101 Background: The immunogenic cancer testis antigen NY-ESO-1 is expressed in several cancers. While NY-ESO-1 is not expressed in vital tissues, it is expressed in approximately 60% in advance myeloma (MM), 15% of ovarian (OC), 32% of advanced melanoma (Mel), 32 % in NSCLC, and 70% of synovial sarcoma (SS) tumors (based on TCGA). Expression is correlated with tumor proliferation and high risk features. An autologous T cell product bearing human-derived affinity-optimized T cell receptor (TCR) which recognizes the SLLMWITQC-HLA-A*A2 peptide complex (NY-ESO-1c259-T) is investigated in several clinical trials Methods: Six clinical studies across 5 tumor types were initiated in HLA-A*02:01 positive patients (pts) with NY-ESO-1 expressing tumors. Fifty three pts have been treated with NY-ESO-1c259-T as of Jan 2016; 27 in MM and 26 in solid tumors. NCT01352286: phase I/II study in post-ASCT setting in pts with relapsed or refractory MM: 25 pts enrolled. NCT01892293: phase I/IIa non-transplant study in pts with relapsed or progressive MM: 2 pts enrolled. NCT01343043: pilot study in unresectable, metastatic, or recurrent SS: 16 pts enrolled: cohort 1 completed (n = 12); 2 additional cohorts have been added to evaluate conditioning and antigen level (4 pts treated across these cohorts to date). NCT01567891: phase I study in pts with refractory or platinum resistant OC and/or have received more than 2 lines of prior chemotherapy: 6 patients enrolled. NCT01350401: phase I study in pts with metastatic melanoma: 4 pts enrolled. NCT02588612: phase I/II study in pts with relapsed metastatic NSCLC: no pts enrolled. The main objectives are safety, tolerability, and efficacy. Biomarker objectives include persistence in peripheral of NY-ESO-1c259-T in blood, T-cell lineage and functionality of these cells over time; characterization of cytokine profiles, as well as NY-ESO-1 antigen levels post infusion. Clinical trial information: NCT01352286, NCT01892293, NCT01343043, NCT01567891, NCT01350401, NCT02588612.
Prostate cancer screening with prostate-specific antigen (PSA) test: a clinical practice guideline
Authors: Kari A O Tikkinen, Philipp Dahm, Lyubov Lytvyn, Anja F Heen, Robin W M Vernooij, Reed A C Siemieniuk, Russell Wheeler, Bill Vaughan, Awah Cletus Fobuzi, Marco H Blanker, Noelle Junod, Johanna Sommer, Jérôme Stirnemann, Manabu Yoshimura, Reto Auer, Helen MacDonald, Gordon Guyatt, Per Olav Vandvik, Thomas Agoritsas
Journal: BMJ (2018)

### What you need to know What is the role of prostate-specific antigen (PSA) screening in prostate cancer? An expert panel produced these recommendations based on a linked systematic review.1 The review was triggered by a large scale, cluster randomised trial on PSA screening in men without a previous diagnosis of prostate cancer published in 2018 (box 1).2 It found no difference between one-time PSA screening and standard practice in prostate cancer mortality but found an increase in the detection of low risk prostate cancer after a median follow-up of 10 years. Box 1 ### Results of the CAP Randomized Clinical Trial2 This cluster-randomised trial of 419 582 British men was published in March 2018. After a median follow-up of 10 years, there was no significant difference in prostate cancer-specific mortality in men receiving care by general practices randomised to a single PSA screening intervention compared with men receiving care … RETURN TO TEXT
Review: Liberal oxygen increases mortality in acutely ill adults compared with conservative oxygen therapy
Authors: KoKo Aung
Journal: Annals of Internal Medicine (2018)

Source Citation Chu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet. 2018;391:1693-705. 29726345
Time perception as a novel ultra-short screening tool for distress in cancer patients.
Authors: Nikolay Vladimirov Conev, Ivan Donev, Dragomir Stoyanov, Martina Ivanova, Eleonora Dimitrova, Asen Yanchev
Journal: Journal of Clinical Oncology (2018)

e22123 Background: Perception of time strongly correlates with people’s current emotional state. The aim of this study was to investigate the association between subjective perception of time and level of psychological distress in cancer patients. Methods: Individual prospective perception of time was assessed in 262 chemo-naïve patients with solid tumors by evaluating how fast one minute passes compared to the actual time. The median value (40 sec) was used to group cases into two categories - with fast (≤median) and slow ( > median) perception of time. The National Comprehensive Cancer Network Distress Thermometer was used at the beginning of treatment to evaluate the level of distress on a scale from 0 to 10. Patients scoring 4 and above (51.9%) were considered as having a high level of distress. Results: The perception of time did not differ significantly between patients’ sociodemographic and clinicopathological characteristics. The pattern of time perception distribution significantly changed over levels of distress (p = 0.001). Patients with fast time perception had significantly higher distress level in comparison with those with slower subjective passage of time (4.55±3.1 vs 3.3±2.9, p = 0.001). Receiver operating characteristic (ROC) analysis revealed that at the optimal cut-off value of perception of time, patients with low and high distress level can be discriminated with AUC = 0.60 (95% CI: 0.53-0.67, p = 0.005) and with sensitivity of 62.5% and specificity of 53.2%. Moreover, in multivariate logistic regression model, fast perception of time was an independent predictor of high distress level (OR 1.97; CI: 1.06-2.98, p = 0.029). Conclusions: Perception of time is a novel potent indicator for high level of distress in cancer patients. It is easily performed, time-saving and non-intrusive ultra-short screening tool suitable even for patients who are not willing to reveal their level of distress via direct questionnaires.
Neoadjuvant denosumab treatment of locally advanced giant cell tumor of bone (GCTB).
Authors: Piotr Rutkowski, Louie Gaston, Aneta Borkowska, Silvia Stacchiotti, Giacomo Giulio Baldi, Emanuela Palmerini, Paolo Giovanni Casali, Alessandro Gronchi, Michael Parry, Hans Gelderblom, Stefano Ferrari, P.D.Sander Dijkstra, Andrzej Pienkowski, Robert Grimer
Journal: Journal of Clinical Oncology (2017)

11026 Background: Retrospective study on locally advanced GCTB patients (pts) treated with neoadjuvant Denosumab (Db) outside clinical trials in 6 European reference centers. Methods: From 138 pts (median age 30yrs) with histologically confirmed advanced GCTB treated with Db(2011-2016), we included into analysis 87pts who underwent surgery after preoperative Db. All 87 patients had locally advanced tumors with extensive soft tissue involvement(54) or penetration to joint, not amenable to limb-sparing surgery/primary curettage or with high risk of recurrence. In 39/42(93%) cases diagnosis was confirmed by H3F3Agene mutation. Median follow-up time -22 months. Results: Primary tumor was located in lower limb(54%; n = 47) -mostly in tibia(25%) and femur(23%), upper limb(33%; n = 29), and pelvis/axial skeleton/ribs(13%; n = 11). 68(78%) patients had primary tumors, 19(22%) recurrent tumors after surgery (+/-radiotherapy). Median Db duration was 7months (range 1.5-35months), 17pts received also Db postoperatively. 39(45%) had wide en-bloc resection -WE (+17 implantation of prosthesis), 48(55%) cases had intralesional curettage -C, no extremity amputation. Pts who underwent prosthetic replacement had longer median preoperative Db therapy as compared to pts without prosthesis. All pts demonstrated a response to Db Progression after surgical treatment was observed in 15 pts -13 of them after intralesional curettage (13/48, 27%); 9 patients underwent D re-challenge -all responded. Two-year progression-free survival (PFS; from Db start) rate was 80%, 91% in WE group vs 73% in C group (p = 0.04), one-year PFS (from operation date) rate was 84%: 92% in WE and 79% in C group(p = 0.01). Treatment was well tolerated with only 1 grade 3 toxicity. Conclusions: Our study confirms that Db is active in a neoadjuvant setting with excellent efficacy and short-term tolerability. It implies that neoadjuvant therapy with Db is the option for treatment of initially locally advanced tumors to facilitate complete surgical resection or avoid mutilating surgery. The risk of recurrences after curettage of GCTB following Db raises questions about the optimal duration of preoperative treatment and if Db is indicated postoperatively.
Adherence to oral therapies in metastatic castration resistance (m CRPC) prostate cancer patients: The ADOPTA study.
Authors: Sandra De la LLave, Laura Carpeño, Johanna Benedetti, Joan Carles, Javier Puente, Alvaro Pinto, Enrique Grande, Joaquin Carballido, David Lorente, Enrique González-Billalabeitia, Rafael Morales, Pablo Gajate, Rosario Alfonso, Begoña Pérez-Valderrama, Amparo Sanchez Gastaldo, Fatima Fernandez, Miguel Angel Calleja, Ignacio Duran
Journal: Journal of Clinical Oncology (2017)

e18014 Background: With the increasing use of oral anticancer treatments understanding adherence patterns and patient’s information about therapy has become critical. Enzalutamide (ENZ) and Abiraterone acetate (AA) are orally administered drugs approved for the treatment of mCRPC widely prescribed; however, scarce information is available about treatment compliance and patient’s information about these compounds. This study aims to evaluate the adherence to AA and ENZ and the patient’s drug knowledge in mCRPC patients. Methods: A 20-question survey is being delivered to patients with mCRPC receiving either AA or ENZ in 8 centers across Spain. Questions cover items such as demographics, drug information, adherence and perceived benefits among other topics. Surveying is still ongoing. Results: Fifty patients have completed the survey at this time. Mean age is 72 years (range 58-87), educational level is basic in 56 %. Median duration of treatment was 9,5 months. Adherence reported is very high with 84% of the patients taking 100% of prescribed doses and 100% more than 75%. Treatment compliance does not seem to decrease over time despite only 42% of the patients reported the use of devices to secure adherence. A high compliance correlated with better symptom control. Nonetheless, many areas of improvement have been also identified. About a quarter of the patients (26%) ignored the name of the drug they were receiving and 24% whether or not they were in a clinical trial. Almost all patients were not aware of the planned duration of treatment and 70 % recognized that they did not know the consequences of a bad adherence. Eleven patients (22%) were taking AA with food outside of a clinical trial and three patients (6%) reported inadequate dosage (i.e q 12h). Conclusions: While in other diseases adherence to oral therapies has been identified as a potential limiting factor with impact in efficacy, in our series of mCRPC treatment compliance was high and maintained overtime. Yet, serious patient education pitfalls were identified. Data collection is ongoing and further analysis will be presented.
Mainstreaming BRCA mutation testing for ovarian cancer patients: Addressing health inequalities.
Authors: Danielle Lisa Shaw, Alice Hulbert, Antony Martin, Anna Claire Olsson-Brown, Marie McKay, Maria Baou, Lynn Greenhalgh, Rosemary Lord
Journal: Journal of Clinical Oncology (2018)

e18526 Background: The prevalence of germline BRCA mutations (BRCAm) in patients with high grade ovarian cancer (HGOC) is approximately 18%. In the era of therapeutic PARP inhibition, identifying BRCAm in patients is vital for clinical decision making, beyond the implications for BRCA-associated cancer screening. NICE guidance (June 2013) recommends testing patients with current or previous HGOC, irrespective of family history or age. To ensure rapid testing of all eligible patients, a regional collaborative pathway between oncology and genetics services was implemented in April 2014, in which BRCA testing is mainstreamed within routine oncology clinics. Following appropriate training, oncology clinicians now identify eligible patients, counsel and consent for BRCA testing and convey results. Rapid referral to genetics services is available. Methods: To assess the efficacy and acceptability of this new pathway, a retrospective audit of all eligible patients was carried out using electronic patient record data (n = 275, April 2013-March 2017). Patient satisfaction surveys were completed. The education quintile for patients who underwent BRCA testing was calculated by matching postcodes to the 'Index of Multiple Deprivation', to explore testing accessibility by education quintile. Results: BRCA testing had increased 5.7-fold by March 2017, following implementation of the NICE guidance. 11.2% of tested patients had a BRCAm. The median age of BRCAm patients was 60 years (range 50-80 years). 94% felt an oncology based assessment was appropriate and would not have preferred a genetics review at that stage. Following implementation of the pathway, patients in the lowest education quintile had a significantly higher probability of receiving BRCA testing (OR 2.45, 95% CI, 1.26-4.76). 75 family members subsequently underwent predictive testing, with 32 relatives found to have BRCAm. Conclusions: BRCAm counselling and testing delivered by oncologists provides an acceptable and effective service. Mainstreaming has increased the uptake of testing of patients in the lowest education quintile; reducing health inequalities.
Effect of cytarabine/anthracycline/crenolanib induction on minimal residual disease (MRD) in newly diagnosed FLT3 mutant AML.
Authors: Richard M. Stone, Robert Collins, Martin S. Tallman, Roland B. Walter, Chatchada Karanes, Prapti Arvind Patel, Madhuri Vusirikala, Catherine Callaghan Coombs, Gretchen Olson, Vinay Kumar Jain, Eunice S. Wang
Journal: Journal of Clinical Oncology (2017)

7016 Background: Baseline characteristics such as age &gt;60, WBC&gt;100,000/µL and FLT3/NPM1/DNMT3A+ve are known to be associated with a poor prognosis in AML. Ivey et al. (NEJM 2016) reported that FLT3-ITD+ve patients (pts) who were MRD+ve after 2 cycles of induction chemotherapy were more likely to relapse as compared to those who became MRD-ve (92% vs 35%). Eradication of FLT3+veclones may lead to reduced relapse rates. Crenolanib is a type I FLT3 TKI, which inhibits both FLT3-ITD and TKD mutations. We here report that a single induction cycle of cytarabine/anthracycline/crenolanib leads to MRD negativity by multiparameter flow cytometry (MPF), and low rate of early relapse in pts with newly diagnosed FLT3+veAML. Methods: This abstract includes 29 consecutively treated, newly diagnosed, FLT3+ve AML pts, who achieved CR1 after one course of cytarabine/anthracycline/crenolanib. Pts received 7+3 induction with cytarabine 100 mg/m 2 /d for 7d and either daunorubicin (&lt;60 y: 90 mg/m 2 ; ≥60 y: 60 mg/m 2 ) or idarubicin 12 mg/m 2 for 3d. Crenolanib (100 mg TID) was started on day 9 until 72 h prior to next chemotherapy. Results: 29 pts (15M, 14F), median age 55y (10pts ≥60y) are included. MRD at time of count recovery was assessed by MPF in 25/29 pts. 20/25 (80%) became MRD–ve. With a median follow up of 7mth, 4/25 pts have relapsed (2/5 MRD+ve, 2/20 MRD-ve).Age ≥60 was a risk factor for MRD+ve and relapse. All 4 pts with WBC&gt;100K as well as 5 pts with FLT3/NPM1/DNMT3A+ve AML became MRD-ve after one induction cycle and none have relapsed. Conclusions: These data suggest, in the context of an ongoing trial (NCT02283177), crenolanib in combination with standard induction is associated with a high rate of achieving an MRD negative state by MPF and a low rate of relapse in previously untreated adults with mutant FLT3. Longer follow-up and comparison of MRD data with similar pts treated with standard chemo alone will be necessary to reach more definitive conclusions. Clinical trial information: NCT02283177. [Table: see text]
CK19 combined with contrast-enhanced ultrasound: A prediction model for non-sentinel lymph node involvement in early breast cancer.
Authors: Xingfei Yu, Linyan Zhou, Chenlu Liang, Chen Wang, Yongfeng Li, Yang Yu, Daobao Chen, Chen Yang, Hongjian Yang, Jian Huang
Journal: Journal of Clinical Oncology (2017)

11539 Background: According to Z0011 and AMAROS trials, patients with breast cancer stage cT1~2cN0 and sentinel lymphnode (SLN) 1~2 involvement can avoid axillary lymphnode dissection (ALND). But the risk of non-sentinel lymphnode (nSLN) involvement in those early stage patients is still unclear and it is difficult to predicting the risk before surgery. Our previous study showed CK19 mRNA in peripheral blood had predicative value of nSLN involvement. Also, contrast-enhanced ultrasound (CEUS) is a new effective method exmaming axillary lymph node. We aim to establish a prediction model for nSLN involvement in early breast cancer using CK19 combined with CEUS score. Methods: We identified 119 cases diagnosed early breast cancer (stage cT1~2cN0 and 1~2 SLNs involvement as in Z0011 and AMAROS trials) from Oct 2015 to Nov 2016 in Zhejiang Cancer Hospital. The CK19 mRNA of peripheral blood by RT-PCR and CEUS score of axillary lymph nodes were acquired before surgery. We used logistic regression analysis for filtering out valuable predictive clinical parameters and establishing formulas to calculate the probability of nSLN involvement. Our model was compared with Memorial Sloan Kettering Cancer Center (MSKCC) nomogram, which is one of the most reliable and validated methods for predicting of nSLN. Results: The histological grade, CK19 and CEUS score were screened by logistic regression analysis into the formula to calculate the probability of nSLN involvement. The sensitivity, specificity, total accuracy of this model was 89.13%, 80.82% and 84.03%, respectively. The false negative rate was 10.87%. The model had high quality of consistency (Kappa 0.675, p &lt; 0.01) and goodness of fit (likelihood-ratio test, -2log liklihood = 84.607). The area under curve (AUC) of ROC was significantly higher (P &lt; 0.01) in our model (0.914, 95%CI, 0.863~0.965) than in MSKCC nomogram (0.563, 95%CI, 0.459~0.667). Conclusions: The prediction model based on CK19 and CEUS score has satisfying sensitivity, specificity and accuracy, more effective than MSKCC nomogram. It is a valuable model of evaluating the risk of nSLN involvement in early breast cancer before surgery, picking out the patients who can truly avoid ALND.
Cancer patient experience with financial counseling among participants of an online registry.
Authors: Joanne S. Buzaglo, Melissa F Miller, Clare Karten, Margaret Longacre, Thomas William LeBlanc, Tara J. Schapmire, Yousuf Zafar
Journal: Journal of Clinical Oncology (2016)

e18265 Background: As many as 1 in 5 cancer patients can’t afford treatment as prescribed. Along with longer-term policy and cost interventions, short-term solutions like financial counseling may reduce patient costs. We described the patient experience with financial counseling and examined the relationship with financial impact. Methods: From April-Nov 2015, 496 cancer survivors joined the Cancer Experience Registry and answered questions about financial counseling. Using a 5-point Likert scale, respondents indicated the extent of their financial impact from cancer. We defined financial counseling as (1) speaking to a professional about cost of care (yes/no) and (2) satisfaction with how much your doctor/health care team spoke about financial costs of each treatment (satisfied=quite a bit, very much; not satisfied=not at all, a little bit). We used descriptive statistics and chi-square tests to analyze results. Results: Median age was 60 y; 78% were female, 91% Caucasian, 50% employed part- or full-time, 38% annual income <$60K, 34% ≥$100K. Diagnoses included breast (47%), CLL (10%), prostate (5%), lung (4%). 24% of respondents spoke to a professional about costs, specifically: financial counselors (32%); nurse navigators (26%); or physicians (27%). 33% were satisfied with how much their health care team spoke about costs. 65% were satisfied with their doctor’s explanation of risks and side effects, and 70% with discussion of treatment benefits. Merely speaking with a professional about cost did not change financial impact, but those who reported satisfaction with financial counseling reported less financial impact of cancer (chi2=22.6, p<0.001). Timing of discussion was associated with patient satisfaction (chi2=8.8, p=0.033, see table). Conclusions: Only a minority of patients spoke with a professional about costs. Merely speaking with one’s health care team about cost did not reduce the financial impact of cancer but satisfaction with financial counseling did. Studies on effects of discussion frequency, duration, and timing could result in best practices to reduce financial burden for cancer patients. Satisfied Not satisfied % % At diagnosis 15 14 Before treatment 76 53 During treatment 9 31 After treatment 0 3