tbuckley/cabot-search huggingface dataset:
Tackling burnout in UK trainee doctors is vital for a sustainable, safe, high quality NHS
Authors: Judith Johnson, Chris Bu, Maria Panagioti
Journal: BMJ (2018)

We read the findings of the General Medical Council’s survey on burnout in trainee and trainer doctors with great interest.1 Increasing evidence indicates that doctor wellbeing is a marker of the quality of care delivered to patients. These results therefore raise concerns about patient care. We have shown a consistent link between healthcare staff burnout …
Abstract IA29: Circulating Tumor Cells: A liquid biopsy for SCLC with multiple applications
Authors: Caroline Dive
Journal: Clinical Cancer Research (2018)

Abstract Circulating Tumor Cells (CTCs) are relatively prevalent in SCLC compared to other tumor types and present several research opportunities in a disease where tumor biopsy is challenging, and notably so when repeated sampling is required. Pre-treatment CTC number by the CellSearch platform (CS-CTCs) is prognostic for overall survival and in most patients decreases significantly after cycle 1 of platinum-based chemotherapy. The prevalence and wide dynamic range of CS-CTC numbers makes them an ideal pharmacodynamic biomarker, and their prevalence affords assay development and implementation as a predictive biomarker in upcoming trials of novel treatments. Recently we showed that chemotherapy response could be predicted via single CTC sequencing to generate a CTC copy number signature (Carter et al., Nat Med 2017). SCLC patients’ CTCs are also highly tumorigenic in immune-compromised mice (Hodgkinson et al., Nat Med 2014). CDX mirror patient tumor histology and chemotherapy response. The resultant CTC-derived explant models (CDX) can be generated not only at baseline but also from the same patient at disease progression, allowing studies of the almost universal acquired chemotherapy resistance and insights into the rapid evolution of this dismal disease. CDX are used for therapy testing and biomarker development that can be translated to CTC-based biomarkers in the clinic. CDX allow exploration of SCLC biology as we recently exemplified by the identification of vasculogenic mimicry and its likely role in metastasis (Williamson et al., Nat Commun 2016). CDX tumors can be disaggregated and propagated in culture for more rapid treatment screening and can be genetically manipulated for function testing hypotheses ex vivo and in vivo. Finally, SCLC CTCs can now be cultured directly from the patient sample, offering the potential for real-time treatment testing. In summary, SCLC CTC research can now make a valuable contribution to the worldwide efforts to molecularly profile this recalcitrant tumor at all stages of disease progression and to discover, develop, and implement new treatments for much-needed improved patient outcomes. Citation Format: Caroline Dive. Circulating Tumor Cells: A liquid biopsy for SCLC with multiple applications [abstract]. In: Proceedings of the Fifth AACR-IASLC International Joint Conference: Lung Cancer Translational Science from the Bench to the Clinic; Jan 8-11, 2018; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(17_Suppl):Abstract nr IA29.
Efficacy and safety of apatinib in osteosarcoma lung metastasis.
Authors: Qianrong Wang, Xiaowen Wang, Lei Wen, Jing Zhang, Jingyue Yang, Yan Chen, Hong-Mei Zhang
Journal: Journal of Clinical Oncology (2018)

e23527 Background: For patients with osteosarcoma lung metastatic, especially for those failed in second-line chemotherapy, treatment options are still failed to meet the medical need. As a new tyrosine kinase inhibitor targeting VEGFR-2, apatinib has antitumor activity in osteosarcoma, but the efficacy and safety of apatinib in osteosarcoma lung metastasis has not been reported independently. This study retrospectively evaluated the efficacy and safety of apatinib in patients with osteosarcoma lung metastases and analyzed possible predictors of efficacy. Methods: A total of 15 patients were enrolled between July 30, 2016 and October 30, 2017. Apatinib 500 mg was given for patients initially with body surface area of more than 1.5 m2. For patients with body surface area less than 1.5m2, apatinib at 250mg was initiated and would be increased if no obvious adverse events occurred after 1 week. The treatment continued until disease progression. The dosage was adjusted based on patient's tolerance. Tumor responses were assessed according to the RECIST 1.1 at every 2 cycles (56 days). Results: After 2 cycles treatment, the control rate was 92.8% (12/14), 42.9% (6/14) achieved partial remission, 50% (7/14) achieved stable disease and 7.1% (1/14) got disease progression. By December 30 2017, 6 of 14 (42.9%) patients experienced dose reductions during treatment. The median PFS was 5.4 months (1-17 months). 3 cases achieved partial remission, 4 cases achieved stable disease, 2 cases got disease progression and 5 cases were dead. The most common adverse events were secondary hypertension (50%, 7/14), oral mucositis (35.7%, 5/14), hand-foot skin reaction (50%, 7/14) and proteinuria (42.9%, 6/14). The major grade 3-4 adverse events were hypertension (21.4%, 3/14), oral mucositis (7.1%, 1/14) and hand-foot skin reactions (7.1%, 1/14). Patients who had hypertension and rash within 1 month of treatment seemed to have a trend of longer PFS (7.0 ± 2.28months vs. 4.25 ± 1.07months, p = 0.2568). Conclusions: Apatinib showed effectiveness in treating osteosarcoma lung metastases after second-line chemotherapy, and the toxicities were tolerable. Occurrence of hypertension and rash within 1 month of treatment might be associated with longer PFS.
Canadian profiling and targeted agent utilization trial (CAPTUR/PM.1): A phase II basket precision medicine trial.
Authors: Tanya Skamene, Lillian L. Siu, Daniel John Renouf, Janessa J. Laskin, Philippe L. Bedard, Steven J. M. Jones, Cristiano Ferrario, James Whitlock, Joan Petrie, Patrick Sullivan, Eoghan Ruadh Malone, Dora Nomikos, Bingshu E. Chen, Janet Dancey
Journal: Journal of Clinical Oncology (2018)

TPS12127 Background: Genomic profiling of cancers is increasingly used to refine prognostication and aid in treatment decisions by allowing matching of targeted agents to specific genetic variants. Clinical reports to date suggest that 30-80% of advanced solid tumours harbor potentially actionable genomic variants but difficulties in obtaining matched targeted agents in clinical practice limits the application of precision medicine. CAPTUR is a pan-Canadian trial leveraging existing clinical genomic profiling platforms and the research capabilities of the Canadian Cancer Trials Group (CCTG) to evaluate targeted drug-genetic variant matches in patients with advanced cancers. CAPTUR was developed in collaboration, and plans to share data, with ASCO's TAPUR and the Netherland's DRUP trials. Methods: CAPTUR/PM.1 (NCT03297606) is a multi-centre, open-label, phase II basket trial, matching Canadian patients who have undergone genomic profiling with genetic variants to appropriate targeted agents. Drug matches are drawn from a list of 17 commercially available anticancer agents. Patients must have incurable metastatic solid tumours, multiple myeloma, or B cell non-Hodgkin lymphoma, must have no standard treatment options known to prolong life and must have an actionable genomic variant known to be a target of, or predict sensitivity to, the commercially available targeted anticancer drug. Patients who possess an actionable tumour genetic variant and meet non-drug specific study requirements are entered into the study. A drug-variant match is assigned based on protocol specified matching criteria or input of the Molecular Tumour Board. Determination of the best treatment is then made by physician and patient based on drug-specific eligibility requirements. Cohorts are defined by tumour type, genomic alteration and matched drug treatment. The primary endpoint is response rate, as determined by disease-appropriate objective criteria. Maximum sample size per cohort is 24 patients based on a Simon 2-stage admissible design. Maximum planned number of cohorts is 30 (maximum sample size for the trial of 720 patients). CAPTUR was activated November 2017 and is open to enrolment. Clinical trial information: NCT03297606.
Accelerated melanoma mortality rates among middle-aged white males with tumors of all thicknesses.
Authors: Juliana Berk-Krauss, David Polsky, Jennifer Stein, Alan Geller
Journal: Journal of Clinical Oncology (2017)

e21029 Background: Effective early detection of melanoma remains one of the most crucial strategies in improving patient prognosis, due to the inverse relationship between primary tumor thickness and survival time. However, recent studies have demonstrated the mortality burden of thin melanomas is at least as severe as that of thicker melanomas. Recognizing specific mortality trends among men and women by age and thickness is essential for establishing targeted melanoma screening efforts. Methods: We evaluated Surveillance, Epidemiology and End Results (SEER) data from 2009-2013. Melanoma thickness was divided into four standard categories: 0.01-1.00mm, 1.01-2.00mm, 2.01-4.00mm and &gt; 4.01 mm. Melanoma mortalities were calculated among white men and women by age and thickness. We used a Bayesian analysis to calculate the probability of an individual dying from a melanoma of a given gender, age, and thickness. We then compared these probabilities between men and women. Results: Among white men, the largest increases in mortality rates occurred in the jump from the 45-49 to 50-54 age group at an increase of 68% for 0.01-1.00mm tumors, and from the 50-54 to 55-59 age group at an increase of 91% for 1.01-2.00mm tumors, 71% 2.01-4.00mm tumors and 80% for &gt; 4.01mm tumors. In white women, mortality rates regardless of thickness increased at a slow incremental pace, across all age groups at an average overall rate of 36%. Mortality rates for white men with &lt; 1mm and 1.01-2mm melanomas were comparable within the age groups less than 64 years, as was the case for white women with tumors of these thicknesses. The probability of a man dying was greater than of a woman for any age or thickness category. Conclusions: Melanoma mortality rate trends are nuanced and can vary significantly by age, thickness, and gender. In white men, mortality rates begin to accelerate sharply around the mid-50s age group. Screening efforts should therefore target detecting melanoma in middle-aged males in the in situ or earliest stage.
A phase 3, open-label, multicenter, randomized study to investigate the efficacy and safety of tislelizumab, an anti-PD-1 antibody, versus docetaxel in patients with non-small cell lung cancer who have progressed on a prior platinum-containing regimen.
Authors: Dingzhi Huang, Ziping Wang, Xinmin Yu, Ying Cheng, Jie Wang, Yun Fan, Zhiyong Ma, Jianhua Shi, Yan Yu, Yi Hu, James Song, Fan Xia, Zhirong Shen, Yun Zhang, Yingying Xu, Carrie Condon, Fangniu Shi, Yunfei Zhou, Andrea Pirzkall, Caicun Zhou
Journal: Journal of Clinical Oncology (2018)

TPS3112 Background: Non-small cell lung cancer (NSCLC) accounts for 80–85% of all lung cancers and has a poor prognosis in later stages. Although lung cancers are not typically immunogenic, recent studies of immune checkpoint inhibitors have shown efficacy in patients with advanced NSCLC. Tislelizumab (also known as BGB-A317) is a humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death receptor-1 (PD-1). Furthermore, tislelizumab was specifically engineered to minimize FcgR binding on macrophages, thereby abrogating antibody-dependent phagocytosis, a potential mechanism of T-cell clearance. A first-in-human, phase 1A/1B study (NCT02407990) demonstrated that single-agent tislelizumab was generally well tolerated and showed evidence of antitumor activity in patients with solid tumors, including NSCLC. A recommended phase 3 dose of 200 mg administered intravenously (IV) every 3 weeks (Q3W) has been identified for tislelizumab. Methods: This phase 3, randomized, multicenter study (NCT03358875) was designed to evaluate the efficacy, safety, and tolerability of tislelizumab compared with docetaxel in the second- or third-line treatment of NSCLC. Adult patients aged ≥18 years with locally advanced or metastatic NSCLC (Stage IIIB or IV, squamous or non-squamous), who have progressed on ≥1 prior platinum-containing therapy, have adequate hematologic and end-organ function, and an ECOG score ≤1 are eligible to enroll. Patients with a known EGFR sensitizing/driver mutation or ALK rearrangement are excluded. Approximately 800 patients from ~100 global clinical sites will be randomized (2:1) to receive tislelizumab 200 mg IV Q3W or docetaxel 75 mg/m2 IV Q3W. Randomization will be stratified by histology, line of therapy, and PD-1 ligand tumor cell expression ( < 25% vs ≥25% [PD-L1+]). Co-primary endpoints are overall survival in the intent-to-treat population and in the PD-L1+ population; secondary endpoints include objective response rate and health-related quality-of-life outcomes. Clinical trial information: NCT03358875.
P05.13 Long term clinical outcomes with helical tomotherapy based image guided intensity modulated radiotherapy for benign and low grade brain tumours
Authors: M P Maitre, T Gupta, R Krishnatry, J S Goda, S Epari, G Chinnaswamy, A Moiyadi, R Jalali
Journal: Neuro-Oncology (2018)

To report long term clinical outcomes of patients with residual, recurrent or progressive benign and low grade brain tumours, treated with helical tomotherapy (HT) based image-guided intensity-modulated radiation therapy (IG-IMRT). Patients with residual, recurrent, or progressive benign/low grade intracranial tumours, treated with HT based IG-IMRT at our institution from 2008–2017 were included in this study. All patients underwent comprehensive baseline neurological assessment before RT. RT planning CT scan of every patient was co-registered with magnetic resonance imaging (MRI) for target volume delineation. HT based IMRT planning was used to achieve highly conformal target volume coverage and minimized dose to critical normal structures in close proximity. Daily setup verification was done for every patient using on-board megavoltage imaging. Patients were followed up clinicoradiologically with serial MRI scans. Tumour control was defined as lack of evidence of tumour progression on serial imaging. Progression was defined as either imaging-defined or clinically observed sustained neurologic worsening. 160 patients (76 males, 84 females) were eligible for analysis, with median age at RT being 37 years (range 5–72 years). Most common diagnoses were meningioma (n=70, 44%), pituitary adenoma (n=27, 17%), craniopharyngioma (n=17, 11%), schwannoma (n = 15, 9%) and optic pathyway glioma (n=13, 8%). Tumour location was sellar/suprasellar in 41%, cerebral hemispheric in 30%, and skull base in 22% patients. Indications of RT included postoperative RT for residual disease (51%), RT for recurrent/progressive disease (28%) and radical RT for inoperable disease (20%). 93% patients had undergone some form of surgical excision before RT. All patients had good Karnofsky performance status (median KPS = 90). 43 % patients had pre-existing neurological deficits before starting RT, including tumour-induced as well as post-surgical deficits. Median planned radiotherapy dose was 54 Gy in 30 fractions. Post RT acute toxicities were mild and self-limiting, with no reported grade III/IV toxicity. 92% patients showed improved or stable neurological deficits following RT. On follow-up imaging, 88% lesions were stable or decreased in extent compared to pre-RT scan, while 12% showed radiological progression. With a median follow-up duration of 47 months, 5-yr OS was 94% and 5-yr DFS was 84%. 5 patients underwent re-surgery and 3 underwent reirradiation for recurrent disease. Late morbidities included stable cranial nerve palsies (29%), motor deficits (8%) and cataract (2.5%). Presently 148 (92.5%) patients are alive and free of disease on regular followup. Use of HT based IG-IMRT in benign and low grade tumours of brain and skull base is effective in achieving durable control with low acute and late morbidity in these long-term survivors.
TCT-856 Peri-coronary Adipose Tissue Expresses Pro-inflammatory Activity, which may Affect Coronary Atherosclerosis In Patients With Coronary Artery Disease
Authors: Tomasz Mazurek, Adam Arendarczyk, Agnieszka Gromadka, Karolina Malesa-Tarasiuk, Marta Koblowska, Radosław Wilimski, Paweł Czub, Krzysztof Filipiak, Piotr Zielenkiewicz, Grzegorz Opolski
Journal: Journal of the American College of Cardiology (2018)
Analysis of serum vitamin D levels and prognosis in stage III colon carcinoma patients treated with adjuvant FOLFOX+/- cetuximab chemotherapy: NCCTG N0147 (Alliance).
Authors: Frank A. Sinicrope, Qian Shi, Thomas C. Smyrk, Richard M. Goldberg, Erica N Heying, Steven J. Cohen, Sharlene Gill, Morton S. Kahlenberg, Suresh Nair, Anthony Frank Shields, Daniel J. Sargent, Balkrishna N. Jahagirdar, Michael N. Pollak, Steven R. Alberts
Journal: Journal of Clinical Oncology (2017)

3516 Background: Epidemiological data suggest a protective effect of vitamin D on CC risk. However, association of serum vitamin D level with clinical outcome in pts with surgically resected CC remains unknown. We analyzed total circulating 25-hydroxyvitamin D [25(OH)D)] with clinical outcome in pts with resected stage III CC treated with FOLFOX +/- cetuximab in a phase III trial. Methods: Association of pre-treatment level of plasma 25(OH)D with disease-free survival (DFS) and time-to-recurrence (TTR) was analyzed with 25(OH)D as a continuous variable by a relative risk model with splines and as a binary variable (vitamin D deficient [&lt;30 ng/mL]) using multivariable Cox regression. Results: Overall, 49% (291/600) of pts were vitamin D deficient. Prevalence of vitamin D deficiency was significantly higher in women vs men (52% vs. 48%, p=0.030) and in blacks vs whites (74% vs. 45%, p=0.0003). The continuous 25(OH)D level and pt sex were associated by the interaction test (p interaction =0.044). There were no statistically significant associations with DFS/TTR for either continuous 25(OH)D level (DFS, p=0.22; TTR, p=0.26) nor for vitamin D deficiency (DFS, adjusted hazard ratio [HR adj ]=1.01, 95% CI, 0.74-1.38; p adj =0.94; TTR, HR adj =1.00; CI, 0.72-1.38; p adj =0.99. A comparison of the highest vs lowest tertile showed a significant association between the highest 25(OH)D level and better outcomes in men (DFS, HR adj. =0.18, CI, 0.04-0.76, p adj =0.020; TTR, HR adj. =0.12, CI, 0.02-0.64, p adj =0.014), but not in women (DFS, p interaction =0.039; TTR, p interaction =0.033). Conclusions: Nearly one-half of pts in the clinical trial cohort were vitamin D deficient with lowest 25(OH)D levels found in women and blacks. While vitamin D deficiency was not associated with adverse outcome, high levels of vitamin D in men, but not women, were associated with longer survival. Support: U10CA180821, U10CA180882, U10CA180820, U10CA180863, U10CA180888, U10CA077202, CCSRI 021039. ClinicalTrials.gov Identifier: NCT00079274.
Racial disparity in oncologic and patient-reported quality of life (PROs) outcomes in patients with locally advanced head and neck squamous cell carcinomas (HNSCC) enrolled in a randomized phase II trial.
Authors: Margaret Winn Kendrick, Mary Weber Redman, Kelsey K. Baker, Renato G. Martins, Keith D. Eaton, Laura Quan Man Chow, Rafael Santana-Davila, Christina S. Baik, Bernardo H. L. Goulart, Sylvia Mina Lee, Cristina P. Rodriguez
Journal: Journal of Clinical Oncology (2016)

6048 Background: Using PROs from our previously completed clinical trial (NCT00410826), we conducted an exploratory analysis to identify PRO associations with clinical factors and oncologic outcomes. Methods: From 12/2006 to 10/2011, 204 patients(pts) were randomized to cisplatin 100mg/m2 on radiation (XRT) days(d)1, 22, and 43 concurrent with 70Gy XRT (Arm A) or the same treatment with erlotinib 150mg daily starting XRT d-7 until XRT completion (Arm B). Using the validated University of Washington QOL form, PROs were measured on XRT d-7 (Arm B only), d0, d30, and d180. PRO associations with clinical factors and oncologic outcomes were explored using linear mixed, logistic and cox models, while adjusting for potential confounders. Results: One hundred eighty nine (93%) [Arm A (N = 97); Arm B (N = 92)] pts consented to PRO collection. PRO scores were available in Arm A: 55 (56%) pts at d0, 65 (67%) at d30, and 45 (46%) at d180 and Arm B: 82 (89%) pts at d-7, 58 (63%) at d0, 69 (75%) at d30, and 41 (44%) at d180. Demographic and tumor characteristics were well-balanced apart from more females in Arm A [20 (19%) vs 8 (8%); p = 0.03]. There were 7 (16%) black pts in Arm A and 13 (13%) in Arm B (p = 0.28). There was no change in mean PRO scores from d-7 on d0 (p = 0.83). Scores were significantly lower in both arms at d30 (estimated difference from baseline -13.21 (CI -18.32, -8.1), with no significant difference by Arm (p = 0.71). D180 remained lower than d-7 for Arm A (estimated difference from baseline -6.56 (CI -12.30, -0.82) p = 0.03), however were not significantly different from d-7 (baseline) in Arm B (p = 0.68). After adjusting for potential confounders on multivariable analysis, black race was an independent predictor for inferior PRO scores [OR -15.87; 95% CI (-21.11, -10.63); p < 0.0001] at all timepoints, complete response rates [OR 0.23; 95% CI (0.1, 0.53); p < 0.001] and overall survival [OR 3.94; 95% CI (1.89, 8.24); p < 0.001]. Conclusions: PRO worsened during chemoradiation, but returned to baseline in pts on Arm B. Black pts had inferior PRO and overall survival, meriting further investigation.