tbuckley/cabot-search huggingface dataset:
Prognostic impact of CDX2 in stage II colon cancer: Results from two nationwide cohorts.
Authors: Torben Hansen, Sanne Kjaer-Frifeldt, Ann Christina Eriksen, Jan Lindebjerg, Lars Henrik Jensen, Flemming Brandt Soerensen, Anders Kristian Moeller Jakobsen
Journal: Journal of Clinical Oncology (2018)

3610 Background: The aim of the present study was to validate the prognostic impact of CDX2 in stage II colon cancer and confirm its clinical potential. Methods: Individual patient data and formalin fixed, paraffin embedded tumor tissue were collected from two unbiased, population-based cohorts representing all patients operated for stage II colon cancer in Denmark in 2002 and 2003. The CDX2 expression was evaluated by immunohistochemistry on whole tumor sections. Patients were classified into three groups, of CDX2 expression: positive, intermediate, and negative, for comparison with the clinical data. The endpoint was disease free survival (DFS). Results: A total of 1,157 patients was included. We found a significant relationship between loss of CDX2 expression and poor DFS in both cohorts, p = 0.0267 and p = 0.0118, respectively. Five-year DFS rates were 66%, 72%, and 74% in the test cohort and 62%, 65%, and 75% in the validation cohort for the negative, intermediate, and positive CDX2 expressing groups, respectively. Multiple Cox regression analysis performed on the combined cohorts confirmed an independent prognostic impact of CDX2 on DFS, hazard ratio 1.543 (95% confidence interval 1.129-2.108), p = 0.0065. CDX2 loss was also associated with an adverse prognosis in patients with tumors harboring microsatellite instability (MSI) (p = 0.0001). Tumors with focal loss of CDX2 expression in the budding cells constituted a specific group with a very poor prognosis, demonstrating a 5-year DFS of only 60%. Conclusions: The present study provides further strong evidence regarding prognostic impact of CDX2 in patients with stage II colon cancer. CDX2 expression should be considered when deciding on adjuvant chemotherapy, especially in the group of patients with MSI tumors.
PD-1 inhibitor treatment of platinum-resistant epithelial ovarian cancer.
Authors: Jan Oldenburg, Marius Normann, Martin Turzer, Olesya Solheim, Lien My Diep, Beata Gajdzik, Erik Rud
Journal: Journal of Clinical Oncology (2018)

e17555 Background: We evaluated the toxicity and clinical efficacy of a programmed cell death (PD-1) inhibitor on patients with platinum resistant ovarian cancer. Further, we explored whether the duration of platinum resistant disease had any influence upon the treatment response. Methods: Every second week, 18 patients with platinum resistant ovarian cancer received a PD-1 inhibitor until disease progression occurred. We assessed toxicity, clinician assessed response rate, disease control rate, progression free- (PFS) and overall survival (OS). The duration of platinum resistant disease prior to PD-1 treatment was registered. Radiological response evaluation was performed every 12th week and clinical evaluation every second week. Results: The clinician assessed response rate was 39%, and the disease control rate was 44%. One patient with radiological stable disease worsened from a clinical point of view. There was 27% reduced chance of responding to treatment for every extra month with platinum resistant disease (OR 0.73, 95% CI: 0.54-0.98). The median OS was 30 weeks (95% CI: 14-42, range 3- 95), and PFS was 15 weeks (95% CI: 9-19). Both were significantly higher among clinical responders compared to non-responders. The median followup time was 30 weeks (range 3-95). Two patients (11%) developed Grade 3 adverse events, while no Grade 4 or 5 events were observed. Conclusions: This study shows few adverse events, and promising clinical efficacy when using PD-1 inhibition for ovarian cancer. It also suggests that a short duration of platinum resistant disease is an important factor for predicting a clinical response.
Assay performance of the PD-L1 IHC 28-8 pharmDx assay in squamous cell carcinoma of the head and neck (SCCHN).
Authors: Sara Alvarez, Debra Ann Hanks, Josette William, Joel A. Chan, Christopher L. Felten, Adam Northrup, Dipeshkumar Jaiswal, Malinka Jansson, Therese Phillips, Andrew Segal, Ilana Satnick, Hendrick McDonald, Hunter Little, Coree Pierce, Bethany Wynne, Josette Carnahan, Swarnalatha Y. Reddy, H. David Inzunza, James Novotny, Emin Oroudjev
Journal: Journal of Clinical Oncology (2017)

e14588 Background: The PD-L1 IHC 28-8 pharmDx assay has been developed for use in detection of PD-L1 protein in formalin-fixed, paraffin-embedded (FFPE) non-squamous NSCLC and melanoma tissues for associated treatment effect with nivolumab. Validation of the assay for measuring PD-L1 expression level in human squamous cell carcinoma of the head and neck (SCCHN) FFPE sections has been conducted and results are described. Methods: Visualization of the PD-L1 IHC 28-8 pharmDx assay is based on the EnVision FLEX IHC technology. As described in the Instructions For Use, antigen retrieval was performed using the Dako PT Link, and the automated staining was conducted with Autostainer Link 48. The assay performance was validated on commercially procured FFPE SCCHN specimens. Results: Assessment of assay sensitivity to PD-L1 expression was measured on 236 unique specimens originating from squamous cell carcinoma of the tongue, tonsil, nasopharynx, oropharynx, hypopharynx, and larynx. The study demonstrated PD-L1 positive staining across a range of 0-95% positive tumor cells and 0 to 3+ staining intensity. Among these tested specimens, 44% of specimens had PD-L1 expression levels ≥1%. Assay robustness was validated by assessing critical parameters such as target retrieval solution pH, target retrieval solution temperature, target retrieval time, and cut section thickness. Assay reproducibility was evaluated in a study at three external sites. Reproducibility of intra-site, inter-day, and inter-site agreement was assessed in addition to inter- and intra-observer agreement. Assay robustness and reproducibility demonstrated agreement estimates above 85% with values for lower bound 95% confidence intervals calculated above 85%. Conclusions: These studies demonstrate that the PD-L1 IHC 28-8 pharmDx assay is reproducible and robust when used for automated detection of PD-L1 protein in FFPE human SCCHN specimens using Autostainer Link 48.
The association between employment changes and healthcare use in the year after cancer diagnosis.
Authors: John F. Dickerson, Jessica Chubak, Borsika Rabin, Larissa Nekhlyudov, Alexandra M Varga, Monica Fujii, Rebecca Ziebell, Matthew P. Banegas
Journal: Journal of Clinical Oncology (2017)

6551 Background: Employed adults diagnosed with cancer face difficult decisions about continuing/returning to work and intensity of work following diagnosis. We examined the association between employment changes and healthcare use among cancer survivors. Methods: Data on adults enrolled at two health plans (Kaiser Permanente (KP) Colorado and KP Washington), diagnosed with breast, colorectal, lung, melanoma, and prostate cancers between 2003-2008, who responded to a 2013 survey with items on employment patterns following diagnosis were used. Survey data were linked to electronic health record (EHR) data on healthcare use, demographics, and cancer characteristics. Employment status and changes following diagnosis were measured. Multivariable logistic and negative binomial regression models were used to assess associations between employment changes and healthcare use in the year after diagnosis, adjusting for demographic and cancer characteristics. Results: Among 465 cancer survivors with complete survey and EHR data, 225 (48.4%) reported being employed since diagnosis. Among employed survivors, 126 (56.0%) reported making an employment change. Those who made a change were more likely to be female, diagnosed with AJCC stage 3 or 4 cancer, have received chemotherapy or hormone therapy, and had a caregiver (all p &lt; 0.01). The most common employment changes were taking extended paid time off (53.2%), unpaid time off (39.7%), and switching to a flexible schedule (29.4%). Employment changes were made at initial diagnosis (18.3%), during treatment (70.6%), and ≤12 months post-treatment (26.2%); 28.6% made more than one change. Survivors who made an employment change had significantly more oncology visits (IRR = 1.85 [95% CI: 1.14-3.00]) and higher odds of hospitalization (OR = 5.18 [95% CI: 2.50-10.8]), but not primary care visits (IRR = 1.19 [95% CI: 0.94-1.50]) in the year after diagnosis, compared to those who did not make a change. Conclusions: Employment changes among cancer survivors are common and may be associated with treatment intensity and other healthcare use in the year after diagnosis. Prospective studies are needed to assess the impact of employment and healthcare use patterns on health outcomes.
Predictive value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) for patients with advanced HBV-associated HCC.
Authors: Zhan-Hong Chen, Jin-Xiang Lin, Ying-fen Hong, Min Dong, Qu Lin, Xiang-yuan Wu
Journal: Journal of Clinical Oncology (2016)

e15609 Background: Many researches indicate that cancer triggers a systemic inflammatory response, causing changes in circulating inflammatory cells. These inflammatory cells are important in the growth, maturation and differentiation of cells within tumour microenvironment. NLR, PLR, and LMR, have been found to be associated with the oncologic outcomes in renal, colorectal, breast and lung cancer. Few reports have focused on the prognostic value of NLR, PLR and LMR in patients with advanced HCC.We evaluated their predictive value. Methods: From September 2008 to June 2010, 174 patients with HBV-associated advanced HCC without fever or signs of infections were analyzed retrospectively. Patient demographics, tumor characteristics and prognostic scores results were recorded. Univariate and multivariate analyses were performed, using the Cox proportional hazards model. Receiver operating characteristics curves were used to determine prognostic score cutoffs. Results: Univariate analysis identified tumour size, portal vein thrombosis, BUN, WBC, monocyte, platelet, NLR, PLR and LMR as independent prognostic factor in Overall survival(OS) in patients with advanced HCC(P < 0.01 ). The multivariate analysis identified tumour size, portal vein thrombosis, BUN and PLR as independent prognostic factor (P < 0.01 ). The PLR cutoff was 90.5 and had the greatest area under the curve (AUC) of 0.705, followed by NLR(cutoff > 2.58; AUC, 0.605) and LMR (cutoff ≤ 4.52; AUC, 0.567).AUC of PLR had a tendency to be statistically significant than that of LMR(P = 0.0585). There did not exist statistical significance between AUC of PLR and NLR, NLR and LMR. Based on cutoff point of PLR, all patients were dichotomized into either a low PLR group( ≤ 90.5) or a high PLR group( > 90.5). OS of low PLR group was significantly longer than that of high PLR group(P < 0.01 ).Higher PLR level was significantly correlated with portal vein thrombosis and larger tumor size(P < 0.01). Conclusions: PLR may provide a simple, cost-effective and easily measured prognostic marker for advanced HCC patients. Lower Baseline PLR levels indicates better prognosis.
Statin use and survival in patients with metastatic castration-resistant prostate cancer treated with abiraterone acetate or enzalutamide.
Authors: Carlo Buonerba, Guru Sonpavde, Gregory Russell Pond, Martina Pagliuca, Sabrina Rossetti, Gaetano Facchini, Sarah Scagliarini, Bruno Daniele, Piera Federico, Franco Morelli, Giacomo Cartenì, Matteo Ferro, Giuseppe Lucarelli, Teresa Bellelli, Sabino De Placido, Giuseppe di Lorenzo
Journal: Journal of Clinical Oncology (2017)

e16503 Background: Statins have been associated with favorable effects in various solid malignancies. In prostate cancer, statins may synergize with novel anti-androgen agents enzalutamide and abiraterone via pharmacokinetic interactions and by decreasing substrate availability for androgen de-novo biosynthesis. Methods: Medical records of patients with metastatic castration-resistant prostate cancer (mCRPC) between September, 2011 and August, 2016 were reviewed at multiple participating centers. Results: 187 men received abiraterone, while 129 received enzalutamide. Patients treated with enzalutamide had a more advanced disease, with a median overall survival (OS) of 7.8 vs. 18 months in the abiraterone cohort. In the abiraterone cohort, statin use was a statistically significant prognostic factor for longer OS (HR = 0.40, 95% CI = 0.27 to 0.59, p &lt; 0.001) and statin users vs. non users had greater 30% PSA declines rates at 12 wks(77.9 vs. 52.9%, p &lt; .01) In the enzalutamide cohort, statin use was not prognostic for survival or PSA declines. Conclusions: Our study suggests a prognostic effect of statins plus abiraterone but not enzalutamide for mCRPC. The mechanism of this interaction warrants elucidation but may include enhancing the anti-tumor activity of abiraterone as well as cardioprotective effects. [Table: see text]
P5 VASCULAR SMOOTH MUSCLE CELL PLASTICITY IN DISSECTING AORTIC ANEURYSMS
Authors: M Clément, J Chappell, J Raffort, F Lareyre, M Vandestienne, A L Taylor, A Finigan, J Harrison, M R Bennett, P Bruneval, S Taleb, H F Jørgensen, Z Mallat
Journal: Cardiovascular Research (2018)
Sex differences in tolerability to Anti-PD1 therapy: Are we all equal?
Authors: Narjust Duma, Jonas Paludo, Elizabeth Ann Enninga, Siddhartha Yadav, Jesus Vera-Aguilera, Lisa A. Kottschade, Haidong Dong, Alex A. Adjei, Roxana Stefania Dronca
Journal: Journal of Clinical Oncology (2018)

9547 Background: Immune related adverse events (IRAEs) have emerged as a serious clinical problem in the use of immune checkpoint inhibitors. The etiology and risk factors for these potentially life-threatening adverse events remain unknown. Therefore, we assessed sex differences in tolerability to anti-PD1 therapy. Methods: All patients (pts) with metastatic melanoma treated with anti-PD1 therapy at Mayo Clinic Rochester from 2014 to 2017 were reviewed. Ocular melanoma cases were excluded. Kaplan-Meier method was used for time-to-event analysis. Results: 245 pts were identified, 148 (60%) were men, 30 (12%) were premenopausal (Pre-M) (≤52 years) and 67 (27%) were postmenopausal (Post-M) women. Baseline characteristics were similar among groups (Table 1). Pre-M women were more likely to experience IRAEs compared to Post-M women and men (67% vs. 60% vs. 46%, p < 0.04). In 23% of Pre-M women anti-PD1 therapy was discontinued due to irAE (men 12%). Pre-M women were more likely to experience endocrinopathies (35% vs. 10%, p < 0.02) and cutaneous reactions (25% vs. 15%, p < 0.02) compared to men. All cases of diabetic ketoacidosis were observed in Pre-M women (n = 6). No differences in grade ≥3 toxicities were seen across groups. Pts with IRAEs were more likely to have a radiographic response to anti-PD1 therapy regardless of sex (68% vs. 44%, p < 0.002). There was a trend towards better PFS in men with IRAEs compared to men without IRAEs (16.5 months vs. 9.7 months, p < 0.05). Conclusions: Pre-M Women were more likely to experience IRAEs compared to Post-M women and men. An association between IRAEs and response to therapy was also observed. Larger studies are needed to confirm these results and investigate etiologic mechanisms underlying these associations. Characteristics Pre-M % (n) Post-M % (n) Men % (n) p value Liver metastasis 33 (10) 33 (22) 30 (45) 0.91 Lung metastasis 47 (14) 30 (20) 42 (62) 0.16 Prior GM-CSF 43 (13) 27 (18) 18 (27) 0.01 Prior radiation 37 (11) 54 (36) 59 (87) 0.08 Prior chemotherapy 13 (4) 16 (11) 18 (27) 0.79 IRAEs 67 (20) 60 (40) 46 (68) 0.04 ≥3 grade IRAEs 50 (10) 43 (17) 31 (21) 0.12 Discontinuation of anti-PD1 due to toxicity 23 (7) 15 (10) 12 (18) 0.37
Characterisation of the TCR repertoire in NSCLC to reveal the relationship between TCR heterogeneity and genetic heterogeneity that is influenced by mutational load and is associated with disease recurrence.
Authors: Kroopa Joshi, Mazlina Ismail, James L Reading, Marc Robert De Massy, Imran Uddin, Mariam Jamal-Hanjani, Selvaraju Veeriah, Theres Oakes, Yien Ning Sophia Wong, Andrew James Scott Furness, Ehsan Ghorani, Andrew Georgiou, Carmella Beastall, Nagina Mangal, Assma Ben Aissa, Mariana Werner Sunderland, Karl Peggs, Charles Swanton, Benjamin Chain, Sergio A Quezada
Journal: Journal of Clinical Oncology (2018)

12009 Background: The lung TRACERx study is a prospective study exploring the cancer genome evolution of NSCLC. Data analysis from the first 100 patients enrolled into the study has shown an increased risk of recurrence or death associated with intratumoural genomic heterogeneity. The importance of the phylogenetic clonality of cancer neoantigens in predicting overall survival in NSCLC and response to checkpoint blockade is previously reported. Methods: We hypothesised that mutational burden and genomic heterogeneity is reflected in the intra-tumoural T cell receptor (TCR) repertoire. We utilised quantitative high throughput sequencing of α and β chains to explore the TCR repertoire from multi-region tumour specimens, normal lung and PBMC samples from patients within the lung TRACERx study. Results: We observed that the TCR repertoire across multi-region tumour specimens was distinct to that observed in normal lung and PBMC. Intratumoural TCR repertoire heterogeneity was found to reflect genomic heterogeneity and was influenced by the tumour mutational load highlighting the potential importance of antigenic dosing in anti-tumour immunity. Moreover, we observed diversification of the TCR repertoire in late stage tumours and disease recurrence was associated with a heterogeneous intra-tumoural TCR response. Alpha and beta chain TCRs re-constructed from single cell RNA sequencing data obtained from T cells reactive to a truncal neoantigen were distributed across all regions of the tumour. Conclusions: Taken together, these findings demonstrate a heterogeneous spatial distribution of tumour infiltrating lymphocytes amongst patients with NSCLC. Moreover, our data suggest that TCR clones present across multiple regions of the tumour may expand in response to the presence of truncal neoantigens. The observations described are indicative of a dynamic intra-tumoural T cell response related to the diverse mutational landscape observed in NSCLC.
Patient navigation core metrics before and after implementation of a nurse navigation program at CHI St. Francis Cancer Treatment Center: A community based cancer program.
Authors: Mehmet Sitki Copur, Monica McDonald, Yuzhen Zhou, Vicki Hurley, Adriene Tasa, Christine Johnson, Rhonda Evans, Courtney Fuller, Rebecca Hadenfeldt, Megan Schriner, Jami Kezeor, Alexis Woodward, Darla Cleveland, Ryan C. Ramaekers, David Crockett, Dron Gauchan, Douglas Clark, Mary Mickey, Max Norvell
Journal: Journal of Clinical Oncology (2017)

e18040 Background: Patient navigation is an intervention to improve cancer outcomes by facilitating timely access to cancer care. Few comparative data exist about the effects of nurse navigation in core navigation metrics (CNM) in a community oncology setting. Methods: During one-year period of a community-based/patient entry-point navigation program, CNMs of newly diagnosed breast and non-breast cancer patients were collected and compared to that of a demographic and tumor characteristics-matched control group prior to navigation. Electronic medical records and tumor registry data were utilized to gather 10 CNMs and 12-mo survival. Results: 72 breast/107 non-breast newly diagnosed navigated cancer patients were compared to same number of matched patients who did not receive navigation. With navigation, significant improvements were observed in interval time to biopsy, pathologic diagnosis, oncology visit, first treatment, and frequency of ancillary consults in breast cancer group. In non-breast cancer group, significant improvements were observed in all CNMs except interval time to pathology diagnosis. Adherence to guidelines and treatment, and 12-mo survival were not different between two groups. Conclusions: A dedicated community based nurse navigation program can significantly improve CNMs and enhance care in both breast and non-breast cancer population in a community oncology setting. [Table: see text]
Efficacy of treatments in children with relapsed/refractory acute lymphocytic leukemia (r/r ALL).
Authors: Amber L Martin, Simu K. Thomas, Mariana Cota, Yanni Hao, Younan Zhang, Monica Turner
Journal: Journal of Clinical Oncology (2017)

e22001 Background: Pediatric ALL is the most common childhood leukemia, 20% of children relapse after initial complete response (CR) to first-line treatment and the 5-year overall survival (OS) of pediatric r/r ALL patients is only 30%. A systematic literature review (SLR) and meta-analysis (MA) were conducted to determine the effects of treatments for pediatric r/r ALL. Methods: EMBASE, MEDLINE, and CENTRAL databases were searched from 01/01/2000-12/31/2016 using keywords for r/r ALL paired with terms for pediatric patients and relevant treatments to identify studies reporting efficacy and safety data. Proceedings from 2015-2016 oncology conferences were also searched. Statistical analysis was limited to studies with comparable patient populations and treatment regimens. Random-effects MA of single-arm data were performed to determine the OS rate at 6 and 12 months, median OS, and the rate of CR (timepoint not reported) for pediatric r/r ALL patients treated with clofarabine + cyclophosphamide + etoposide (CCE). Results: The studies included in the review were heterogeneous and just five of the 46 studies identified by the SLR were similar enough for MA in terms of outcomes and populations (median age 8-14 years, median 2 prior lines of therapy). All five studies were single-arm studies evaluating CCE, a treatment with a pooled 6-month OS of 43.5% (95% CI: 32.6% - 55.1%), 1-year OS of 26.7% (95% CI: 17.5% - 38.3%), and pooled median OS of 5.2 (95% CI: 3.2 – 8.6) months. The CR rate was 43.2% (33.7% - 53.3%) across the five studies (timepoint not reported), and the rate was comparatively higher when analysis was limited to those with B-cell immunophenotype (56.3% [95% CI: 22.5% - 85.1%]). Conclusions: This is the first SLR and MA to be conducted on pediatric r/r ALL to date. Available evidence was heterogeneous and MA were only possible for single-arm trials examining CCE. Survival is poor in this population, as just over a quarter of patients receiving CCE were alive at 12 months, with median OS less than 6 months. CR rates were more promising but the lack of data on timepoint of assessment make the results difficult to interpret. New treatments are needed to better manage patients in this r/r population.