tbuckley/cabot-search huggingface dataset:
Effects of Radiotherapy in Early-Stage, Low-Recurrence Risk, Hormone-Sensitive Breast Cancer
Authors: Jinani Jayasekera, Clyde B Schechter, Joseph A Sparano, Reshma Jagsi, Julia White, Judith-Anne W Chapman, Timothy Whelan, Stewart J Anderson, Anthony W Fyles, Willi Sauerbrei, Richard C Zellars, Yisheng Li, Juhee Song, Xuelin Huang, Thomas B Julian, George Luta, Donald A Berry, Eric J Feuer, Jeanne Mandelblatt
Journal: JNCI Journal of the National Cancer Institute (2018)

Radiotherapy after breast conservation has become the standard of care. Prior meta-analyses on effects of radiotherapy predated availability of gene expression profiling (GEP) to assess recurrence risk and/or did not include all relevant outcomes. This analysis used GEP information with pooled individual-level data to evaluate the impact of omitting radiotherapy on recurrence and mortality.We considered trials that evaluated or administered radiotherapy after lumpectomy in women with low-risk breast cancer. Women included had undergone lumpectomy and were treated with hormonal therapy for stage I, ER+ and/or PR+, HER2- breast cancer with Oncotype scores no greater than 18. Recurrence-free interval (RFI), type of RFI (locoregional or distant), and breast cancer-specific and overall survival were compared between no radiotherapy and radiotherapy using adjusted Cox models. All statistical tests were two-sided.The final sample included 1778 women from seven trials. Omission of radiotherapy was associated with an overall adjusted hazard ratio of 2.59 (95% confidence interval [CI] = 1.38 to 4.89, P = .003) for RFI. There was a statistically significant increase in any first locoregional recurrence (P = .001), but not distant recurrence events (P = .90), or breast cancer-specific (P = .85) or overall survival (P = .61). Five-year RFI rate was high (93.5% for no radiotherapy vs 97.9% for radiotherapy; absolute reduction = 4.4%, 95% CI = 0.7% to 8.1%, P = .03). The effects of radiotherapy varied across subgroups, with lower RFI rates for those with Oncotype scores of less than 11 (vs 11-18), older (vs younger), and ER+/PR+ status (vs other).Omission of radiotherapy in hormone-sensitive patients with low recurrence risk may lead to a modest increase in locoregional recurrence event rates, but does not appear to increase the rate of distant recurrence or death.
Overall survival in stage II prostate cancer after radiation or surgical therapy.
Authors: Sydney Marsh, Ryan W Walters, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2016)

5068 Background: A recent study of 13,803 men found those treated with external beam radiation therapy (EBRT) had higher prostate cancer specific mortality compared to patients undergoing radical prostatectomy (RP) (Lee BH j.eururo.2014.09.017). We used the National Cancer Database to evaluate survival in patients with stage II prostate cancer treated with EBRT or RP. To our knowledge, our study is the largest to date evaluating these differences. Methods: We analyzed 455,106 men diagnosed with stage II prostate cancer from 2004-2013. Kaplan-Meier estimates and multivariable Cox regression analysis controlling for age, race, Charlson/Deyo (CD) score and PSA level were used to compare survival between treatments. CD score tabulates 0, 1, or 2 comorbidities. Results: We evaluated 169,185 EBRT and 285,921 RP patients. The average age of RP patients was younger than EBRT (60.56 years vs 69.42 years, p< .05) and the average PSA of RP patients was lower than EBRT (7.67 ng/mL vs 11.82 ng/mL, p< .05). White patients were more likely to receive RP than non-white patients (64.5% vs 35.5%, p< .05). 87.2% and 84.6% of EBRT and RP, respectively, had no comorbidities (CD = 0). Unadjusted mean survival was significantly longer for RP than EBRT (124.5 months vs 106.5 months, p < .05). Multivariable Cox regression indicated significantly longer survival for patients who were younger, white, had a lower Charlson/Deyo score and lower PSA. Multivariate analysis favored EBRT at 3 years (HR 2.12, p < .05), while RP provided significantly greater survival at 10 years (HR 0.11, p < .05). RP and CD 0 had the most impact on survival at 10 years. Conclusions: Men treated with RP had lower survival at three years, but significantly higher 10 year survival compared to EBRT. These results imply men treated with RP had higher early mortality but significantly better long term survival. Multivariate analysis of overall survival at 10 years. HR Age 1.061* White 0.887* Charlson/Deyo Scorea 0 0.380* 1 0.603* PSA 1.010* Surgeryb 0.111* Note. *p<.05. HR = hazard ratio; HR below 1 indicates longer survival. aReference CD = 2. bCompared to radiation treatment specifically at 10 years.
Impact of gene expression profiles on clinical predictors of survival in patients (pts) with <i>BRAF</i><sup>V600</sup>-mutated metastatic melanoma (mM).
Authors: James M. G. Larkin, Karl D. Lewis, Antoni Ribas, Keith Flaherty, Paolo Antonio Ascierto, Brigitte Dréno, Edward Francis Mckenna, Qian Zhu, Yong Mun, Axel Hauschild, Grant A. McArthur
Journal: Journal of Clinical Oncology (2017)

9556 Background: Treatment of BRAF V600 -mutated mm with V and C+V has clinical benefit. Prior analyses established PFS/OS prognostic models in pts with mm based on clinical variables. This exploratory analysis evaluated the impact of immune and cell cycle gene signatures (GS) from baseline mm (Wongchenko et al, Pigment Cell Melanoma Res2015;28:822) on survival outcomes and associated prognostic models. Methods: Data from all eligible pts with GS data in the BRIM-2, -3, -7, and coBRIM studies were pooled for analysis. The independent effect of GS on PFS/OS outcomes was tested by multivariate Cox proportional hazards models. Recursive partitioning (RP) for censored response variables in a conditional inference framework was performed in the pooled dataset to model relationships between prespecified covariates, GS, and PFS/OS. Prognostic subgroups identified by the model for all pooled pts were applied to pooled treatment cohorts (dacarbazine [D], V, and C+V). Results: GS data were available for 608 pts across pooled studies. Immune GS was associated with improved survival vs cell cycle for PFS (HR = 0.75, 95% CI 0.62–0.89, P= 0.0015) and OS (HR = 0.74, 95% CI 0.61–0.90, P= 0.0024) in multivariate models. HR point estimates were consistent across treatment cohorts. PFS RP models identified baseline LDH, tumor size, and GS as prognostic factors, giving 4 groups with distinct outcomes. GS was not identified as a prognostic factor in OS RP models. C+V improved PFS/OS outcomes vs V across prognostic subgroups. Immune GS was significantly (one-sided Cochran-Armitage trend test) more prevalent in the favorable prognostic groups previously defined for PFS and OS for the V ( P&lt; 0.0001 for both) and C+V cohorts ( P= 0.0240 and P= 0.0269, respectively), but not the D cohort. Conclusions: PFS/OS was significantly improved for pts with immune GS. RP modeling confirmed the importance of GS as an independent prognostic factor for PFS but not OS. The preferential association of immune GS with favorable prognostic subgroups in the C+V and V but not D cohorts and known effects of MAPK signaling on immune response merit further exploration in prospective studies.
VA oncologists’ attitudes and behaviors regarding genomic-based targeted therapy for the management of advanced lung cancer.
Authors: Jennifer Arney, Ashley Helm, Guoqing J. Chen, Teresa Gray Hayes
Journal: Journal of Clinical Oncology (2016)

e20573 Background: Genomic-based targeted therapy (GBTT) has emerged as a treatment option for patients with advanced lung cancer. Clinical practice guidelines of the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) recommend testing all metastatic adenocarcinomas for EGFR mutation, and use of EGFR-TKIs (erlotinib) as first-line therapy for advanced adenocarcinoma lung cancer patients with EGFR mutation positive. Little is known about how oncologists utilize genomic testing and GBTT in a clinical setting. Drawing from the Cabana, et al. theoretical framework on providers’ adherence to guidelines, this study aims to elicit provider and facility-level barriers and facilitators to using GBTT in VA healthcare delivery system. Methods: We conducted 25 in-depth, qualitative interviews from a sample of VA oncologists from March, 2015 and January 2016. Consistent with the Cabana, et al. framework, interviews sought to elicit oncologists’ knowledge, attitudes, and intent to use GBTT, and barriers and facilitators for practicing GBTT in a VA-setting. Analysis was dictated by thematic saturation. Results: We identified varying degrees of guideline-consistent utilization of genomic testing and GBTT. Oncologists estimated that roughly 20-90% of metastatic adenocarcinomas are tested for a mutation. Many participants had never found a positive mutation and had never used GBTT in a first-line setting. Almost all participants had used GBTT in a second-line setting or as maintenance. Consistent with the Cabana et al. framework, nonadherence to guidelines seems to result from oncologists’ lack of familiarity with guidelines and some barriers, including patient factors, facility resources, and organizational constraints. Conclusions: This is the first study to examine oncologists’ knowledge, attitudes, and experiences with using GBTT in a clinical setting. Findings reveal a need for provider education on genomic testing and treatment guidelines. Further research is needed to fully understand how facility resources–specifically, budgetary issues in the pathology department–shape oncologists’ ability to adhere to testing guidelines.
Evaluation of survival outcome of gastric cancer with pathologic stage III according to the new eighth edition of the AJCC/UICC TNM classification.
Authors: Etsuro Bando, Rie Makuuchi, Sanae Kaji, Makoto Hikage, Tomoyuki Irino, Masanori Tokunaga, Yutaka Tanizawa, Taiichi Kawamura, Yusuke Kinugasa, Teiichi Sugiura, Katsuhiko Uesaka, Masanori Terashima
Journal: Journal of Clinical Oncology (2017)

e15536 Background: Postoperative adjuvant chemotherapy with administration of S-1 for one year is standard treatment in patients with pStageII/III in Japan. However, survival outcome of patients with pStageIII remains unsatisfactory, so several attempt have been made to improve the survival in these patients. However, actual survival according to sub-classification in pStage III has not been elucidated. The eighth edition of the American Joint Committee on Cancer (AJCC) TNM postoperative staging for gastric cancer was published in 2016 and included major revisions of pStageIII. The aim of the current study was to evaluate the validity of the eighth edition TNM classification, especially in pStageIII for gastric cancer based on patients treated in single Japanese high volume cancer center. Methods: A total of 646 gastric cancer patients with pStageIII who underwent R0 resection from 2002 to 2016 were included. Prognostic value was analyzed for validation and compared TNM seventh edition. Results: Some improvement was observed in the separation of pN. Patients with pN3b (5-year survival rates = ysr; 13.4%) had the significant poor survival than those with N3a (5-ysr; 39.1%) (P &lt; 0.001). In pStage III disease, clear survival distribution was observed in eighth edition [IIIA (N = 315); 5-ysr: 67.0%, risk ratio (RR) = 1 (reference), IIIB (N = 230); 5-ysr: 51.1%, RR = 1.694, P &lt; 0.001, IIIC (N = 101); 5-ysr: 30.9%, RR = 2.771, P = 0.002], compared to seventh edition [IIIA (N = 233); 5-ysr: 69.3%, RR = 1;, IIIB (N = 230); 5-ysr: 53.8%, RR = 1.682, P = 0.001, IIIC (N = 183); 5-ysr: 38.7%, RR = 2.571, P = 0.004]. Conclusions: Survival outcome of pStageIIIC (T3-T4bN3b, T4bN3a) in eighth edition is very poor. So, more aggressive regimen should be planned for pStageIIIC gastric cancer in eighth TNM staging.
Establishment of a “near patient model” of dedifferentiated liposarcoma: A proof of concept of the usefulness of zebrafish model.
Authors: Chiara Liverani, Laura Mercatali, Federico La Manna, Arwin Gronewoud, Gabri Van der Pluijm, Ewa Snaar-Jagalska, Federica Pieri, Davide Cavaliere, Alessandro De Vita, Chiara Spadazzi, Giacomo Miserocchi, Alberto Bongiovanni, Federica Recine, Nada Riva, Dino Amadori, Toni Ibrahim
Journal: Journal of Clinical Oncology (2016)

e23190 Background: Patient-derived specimens are an invaluable resource to study cancer in particular in rare tumors as Soft Tissue Sarcomas, for which several subtypes exist, that are not all covered by the matched cancer cell lines. Here we present data obtained on a primary culture of a dedifferentiated liposarcoma treated with chemotherapy and injected into the zebrafish model as the proof of concept of the usefulness of near patients models in the study of cancer cells aggressiveness and responsiveness to drugs. Methods: Primary dedifferentiated liposarcoma cells isolated from patient undergoing surgery were cultured on 3D collagen scaffolds as well as on 2D conventional supports. Cells were treated with trabectedin and with the standard combination ifosfamide and epirubicin. Aggressiveness markers were assayed by qPCR. Cells were injected in the heart cavity of zebrafish embryos, monitoring the embryos daily. Results: The 3D tumor model were enriched for cancer cells, as demonstrated by a higher percentage of MDM2-positive primary dedifferentiated liposarcoma cells respect to 2D cultures (55% vs 5%) and preserve liposarcoma-associated markers as β-catenin, MMPs and ALDH1.Chemotherapy proved effective on 3D-enriched liposarcoma cells with percentages of survival significantly lower to controls, and not significantly different between epirubicin plus ifosfamide and trabectedin alone, being respectively 48% and 53%. Liposarcoma cells injected in zebrafish were capable of surviving in the heart cavity and in later stages were scattered throughout the implantation area showing local migratory and invasive abilities, and the successful engraftment of this patient-derived liposarcoma culture in this animal model. Conclusions: The implementation of synergistic in vitro and in vivo models has allowed us to observe the aggressiveness abilities of a liposarcoma primary culture. We demonstrated in vitro a similar efficacy of trabectidin respect to the conventional first line therapy epirubicin plus ifosfamide opening new horizons to better investigate the mechanism of action of these drugs and the treatment strategy of dedifferentiated liposarcomas.
FRI0093 Don’t miss the depression! comorbidities in patients with rheumatoid arthritis and their impact on patient-reported outcomes: results of claims data linked to a questionnaire survey
Authors: K. Albrecht, A. Luque Ramos, J. Callhoff, I. Redeker, F. Hoffmann, A. Zink
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Comorbidities are increasingly acknowledged as important clinical manifestation in patients with rheumatoid arthritis (RA). <h3>Objectives</h3> To investigate the prevalence of comorbidities in RA and their association with patient-reported outcomes. <h3>Methods</h3> Data of 96 921 persons with RA and 4 84 605 age- and sex-matched controls of a German statutory health fund were studied on the presence of selected comorbidities in 2015. Diagnoses and therapies were assigned to the provider (general practitioner, rheumatologist or another specialist). A self-reported questionnaire, comprising joint counts (TJC, SJC), functional status (FFbH), impact of the disease (RAID) and well-being (WHO-5) was sent to a random sample of 6195 persons with RA of whom 3184 responded. For respondents who confirmed their RA (n=2,535), the association between comorbidities and patient-reported outcomes were analysed by multivariable linear regression analyses. <h3>Results</h3> Compared to controls, persons with RA (mean age 63 years, 80% female) had higher prevalences of all comorbidities, the most common were depression and osteoporosis besides cardiovascular risk factors (table 1). The diagnosis of depression was provided in 50% of cases by general practitioners, in 13% by rheumatologists and in 48% by other specialists while the diagnosis of osteoporosis was made in 76% by general practitioners, in 48% by rheumatologists and in 46% by other specialists. Among the survey respondents, increasing numbers of comorbidities were associated with worse TJC, SJC, function and WHO-5 values. Depression, obesity and osteoporosis had the highest impact on functional status and TJCs. The percentage of patients in rheumatologic care decreased from 73% with 0–1 comorbidity to 62% with ≥8 comorbidities (age-adjusted). <h3>Conclusions</h3> Osteoporosis and depression are amongst the most common disorders in persons with RA. While osteoporosis is usually taken into account by the rheumatologist, more attention should be paid to depression as both disorders strongly affect patient-reported outcomes. <h3>Acknowledgements</h3> This study was funded by the German Federal Ministry of Education and Research (01EC1405). <h3>Disclosure of Interest</h3> None declared
TCT-283 Increase in carotid inflammation in patients with CAD independently predicts two-year MACE
Authors: Georgios Benetos, Konstantinos Toutouzas, Iosif Koutagiar, None George Oikonomou, None Maria Karmpalioti, Nikolaos Barampoutis, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2018)
Impact of a natural language processing (NLP) tool on patient identification, navigator efficiency, and time to first treatment.
Authors: Brook Blackmore, Crystal Dugger, Troy Gifford, Dax Kurbegov
Journal: Journal of Clinical Oncology (2018)

e18512 Background: Sarah Cannon has established a standardized nurse navigation program for breast, lung, and GI cancer patients. Navigators play a significant role in addressing barriers that may adversely impact patient outcomes. Facilitating referral of newly diagnosed cancer patients to the navigator is a barrier in the community setting. Historically, nurse navigators spend up to 65% of their time data mining to identify new patients for navigation. This lost time compromises a navigator’s ability to effectively support patients. Sarah Cannon implemented a technology solution to address this manual process. Methods: A patient identification software tool (Patient ID), utilizing NLP technology, was developed to identify positive pathology reports across the enterprise in real time. Patient ID instantly routes those reports to a tumor site-specific oncology nurse navigator. The impact of this technology was assessed in three Hospital Corporation of America (HCA) markets from December 2015-March 2016. Total patient recall, total volume of reports reviewed, navigated patient volumes, navigator time allocation, and time from diagnosis to first treatment were studied. Results: Patient ID reviewed 47,544 pathology reports during the four-month pilot, identifying 7,224 potential cancer reports. 2,782 of those represented breast, lung, or GI cancer patients and were routed to a nurse navigator. Patient ID identified 98% of relevant reports (recall). Decreased time spent data mining was observed, and navigator caseload increased by 71%. Time from diagnosis to first treatment decreased by an average of 6 days. Time allocated to direct patient contact and physician interaction increased by 35%. Conclusions: Implementation of a technology solution to rapidly identify new cancer patients for navigation in a community health system is feasible and associated with multiple benefits. Increased navigator patient volumes and navigator productivity were observed. Navigator time spent with patients and physicians increased with a concurrent reduction in data mining time. Timeliness of care metrics improved, suggesting a favorable impact on quality.
The risk of malnutrition in patients with rectal carcinoma: An analysis of 9789 patients.
Authors: Carl Meissner, Joerg Fahlke, Ronny Otto, Christoph Kahl, Henry Ptok, Walter Asperger, Hans Lippert, Karsten Ridwelski
Journal: Journal of Clinical Oncology (2017)

e15059 Background: The problem of under-nutrition and lack of nutrition is increasingly placed in the focus of operational discipline. Many of them are deficient in malnutrition before being hospitalized. In surgical therapy, the prevention of postoperative complications is of utmost importance. Due to a preoperative condition of malnutrition, the complication rate may increase and thus the associated increased treatment therapy costs per patient. The consequence, of course, is also a diminished postoperative treatment quality of the treating clinic. Methods: Prospective Multicentre Observational Study: "Quality Assurance Study of Rectal Cancer from 2010-2014 of the" An-Institute for Quality Assurance in Operative Medicine "at the Otto-von-Guericke-University Magdeburg, was screened for Nutritional Risk Screening (NRS 2002) Kondrup J et al Results: 9789 primary data records from 2010 to 2014 were included. With the help of the NRS screening, a total score in the form of a scoring system is possible. The sum of 3 points or more identifies a patient with a food-related risk and should be a cause for further diagnosis and therapy. The median of all rectal carcinoma patients was NRS = 3. 53.9% of the patients had an NRS score of &gt; = 3. In morbidity, the complications in colorectal cancer patients with NRS &gt; = 3 points are significantly increased. Also in the case of general complications (such as pneumonia, urinary tract infection, etc.) the rate increases with a larger NRS score. Conclusions: If the risk of malnutrition is small in patients with a colon carcinoma, the morbidity is low.
Model combining genomic and clinical factors to predict clinical benefit from PD1/PD-L1 inhibitors for advanced UC.
Authors: Amin Nassar, Kent William Mouw, Chia-Jen Liu, Kevin Lundgren, Eliezer Mendel Van Allen, Lauren Christine Harshman, Mark Pomerantz, Mark A. Preston, Xiao X. Wei, Bradley Alexander McGregor, Atish Dipankar Choudhury, Joaquim Bellmunt, Toni K. Choueiri, David J. Kwiatkowski, Guru Sonpavde
Journal: Journal of Clinical Oncology (2018)

4539 Background: Tumor mutational burden is associated with response to PD1/PD-L1 inhibitors in advanced UC. We explored the ability of copy-number variants (CNVs) and specific genomic alterations to complement single-nucleotide variants (SNVs) to predict clinical benefit in patients (pts) with advanced UC receiving PD1/PD-L1 inhibitors. Methods: Targeted exome sequencing (238 genes) was performed on archival tumors from metastatic UC pts treated with PD1/PD-L1 inhibitors at our institution. Clinical Benefit (CB) was defined as any objective reduction in tumor size, and no clinical benefit (NCB) was defined as any objective increase in tumor size by RECIST 1.1. Associations between clinical and genomic features and clinical benefit were assessed using univariate and multivariate logistic regression modeling. Results: 61 pts were evaluable, with CB in 24 pts and NCB in 37 pts. The prognostic factors associated with NCB on univariate analysis were neutrophil/lymphocyte ratio (NLR) ≥5, ECOG-PS ≥1, hemoglobin (Hb) < 10 gm/dl, liver metastasis, CDKN2B homozygous deletion, high CNV count and low SNV count. On multivariate analysis, a low SNV count and a high CNV count were associated with NCB. There was a strong trend for association of NCB with liver metastasis and NLR ≥5 (Table). Conclusions: A new model combining 2 genomic factors, low SNV and high CNV counts, and 2 clinical factors, high NLR and liver metastasis, appeared associated with NCB in pts with advanced UC receiving PD1/PD-L1 inhibitors. Validation of these hypothesis-generating results is warranted. Risk factors Adjusted OR p value Liver metastasis 7.78 (0.84–71.85) 0.070 CDKN2B homozygous deletion 4.61 (0.24–90.06) 0.314 NLR ≥ 5 9.17 (1.00–84.33) 0.050 ECOG-PS ≥ 1 0.76 (0.12–4.92) 0.775 Hb < 10 gm/dl 7.60 (0.22–258.88) 0.260 CNV count ≥ 1 (median) 8.80 (1.02–76.39) 0.049 SNV count < 8 (median) 12.39 (1.65–92.85) 0.014