tbuckley/cabot-search huggingface dataset:
Using a geriatric oncology assessment to link with services in an underserved, community oncology population.
Authors: Leah L. Zullig, Gretchen Genevieve Kimmick, Valerie Smith, Katie Little, Hayden B Bosworth, Sarah Gonzales, Megan Oakes, Rebecca A. Shelby, Lynda Owen, Linda Sutton, Ivy Altomare
Journal: Journal of Clinical Oncology (2018)

e22024 Background: By 2030, most cancer cases will be diagnosed among older adults, who are more likely to have functional limitations. Geriatric oncology assessments (GOAs) can be used to assess these limitations and inform clinical decision-making. Despite supporting evidence, GOAs are not widely used, especially in community clinics. Our objective was to evaluate the feasibility and effectiveness of a brief GOA and explore associations with treatment completion. Methods: Eligible patients from 2 rural, underserved community-based cancer clinics were within 6 months of a cancer diagnosis (breast, lung, colorectal, pancreas, esophageal); aged ≥60 years at enrollment; and were not pursuing only palliative care. The brief GOA is a validated ~16-item tool adapted from Overcash et al 2006 and embedded in the electronic health record (EHR). Item responses identified memory impairment, depression, deficits in ADL, poor nutrition, and polypharmacy and prompted referrals to support services, at the discretion of the oncologist. Planned and actual treatment was determined from the EHR. Results: Our 44 enrolled patients had a mean age of 71.5 years (SD = 6.9). Approximately half were married (48%), non-white (61%), women (66%) with breast cancer (57%). Most patients were diagnosed with non-metastatic disease (82%), and received chemotherapy (80%). Most common impairments were polypharmacy (89%), present quality of life (39%), or poor nutrition (39%). The results of the GOA triggered a referral in 98% of patients. Generated referrals were for: depression (52% needed, 39% received), nutrition (43% needed, 37% received), and polypharmacy (89% needed, 26% received). Patients were most commonly referred to social work (56%), nutrition (44%), pharmacy (25%), and/or mental health (20%). All patients completed planned radiation therapy. Many patients completed planned surgery (70%) and chemotherapy (60%). Conclusions: Use of an EMR-embedded brief GOA in rural oncology clinics identified geriatric syndromes that would benefit from provision of services in nearly all enrolled patients. Our future work will compare referral rates and outcomes to matched control patients. Clinical trial information: NCT02906592.
TCT-594 Rotational atherectomy and the risk for contrast-induced nephropathy
Authors: Ozan Demir, Francesca Lombardo, Enrico Poletti, Alessandra Laricchia, Alessandro Beneduce, Davide Maccagni, Massimo Slavich, Francesco Giannini, Mauro Carlino, Alberto Margonato, Alberto Cappelletti, Antonio Colombo, Lorenzo Azzalini
Journal: Journal of the American College of Cardiology (2018)
Effect of radiation dose escalation on outcomes in patients with N2 stage IIIA NSCLC undergoing induction therapy prior to surgical resection.
Authors: Greg Andrew Durm, Susan Perkins, Shadia Ibrahim Jalal, Feng-Ming (Spring) Kong, Thomas J Birdas
Journal: Journal of Clinical Oncology (2018)

8513 Background: For pts with resectable stage IIIA NSCLC, one accepted tx option is induction therapy with concurrent chemoradiation followed by surgical resection in selected pts. However, the appropriate dose of radiation (RT) has remained largely unanswered. Full dose RT has been reported to be safe and is often used in clinical practice. We conducted a National Cancer Database analysis to compare outcomes between dose escalation vs. conventional dose RT during induction therapy in patients with T1-T3, N2, M0 NSCLC tx with surgical resection. Methods: We queried the NCDB between 2006-2014 for pts with T1-T3, N2, M0 NSCLC undergoing curative surgery after induction therapy. We compared the short-term postoperative outcomes and long-term survival based on RT dose groups. Group 1: standard dose (45-50.4 Gy, 67%), Group 2: high dose ( > 50.4 Gy 33%). Statistical analysis was performed using SAS v9.4, and p < 0.05 was considered to be significant. Results: 2499 pts met inclusion criteria. High dose RT was significantly more common in academic centers, in later years, and left-sided tumors in the database, but not related to age, race, sex, Charlson Comorbidity Index (CCI) or type of surgery performed. Perioperative outcomes (length of stay, 30- and 90-day mortality) were not significantly affected by RT dose. Mediastinal sterilization ( < pN2 disease) increased significantly with dose escalation as did path CR rates, but median and 5-year survival did not (Table, with 95% CIs). In multivariate analysis, long-term OS was significantly higher in men, younger age, lower CCI and lobectomy, but not affected by RT dose (even if treated as a continuous variable). Conclusions: In pts with clinical stage IIIA NSCLC treated with induction concurrent chemoradiation, RT dose escalation resulted in increased mediastinal sterilization and pCR rates, but it did not change perioperative mortality or long-term OS. 2004-2014 N 5yr-OS (%) Median OS (mo) Mediastinal sterilization (%) pCR (%) 45 to 50.4 Gy 1677 46.2 (43.4,49.1) 48.6 (42.6, 56.0) 51.1 (48.6,53.5) 13.3 (11.7,15.1) Above 50.4 Gy 822 46.4 (41.7,50.9) 55.1 (42.8, 62.4) 61.0 (57.5,64.4) 18.5 (15.8,21.4) p-value .71 < 0.001 < 0.001
Co-mutations in surgically resected and EGFR mutated lung adenocarcinoma: A subset analysis of the large prospective cohort study.
Authors: Kenji Sawa, Tomoya Kawaguchi, Yasuhiro Koh, Akihito Kubo, Akihiro Tamiya, Naoki Yoshimoto, Shun-ichi Isa, Hideo Saka, Akihide Matsumura
Journal: Journal of Clinical Oncology (2018)

e20520 Background: Several studies including LUX LUNG 3 and 6 have shown that there are biological differences between EGFR exon 19 deletions (del19) and exon 21 L858R mutation (L858R) in lung adenocarcinoma (AD). It is suggested that coexisting mutation or co-mutations status can play a major role in the discrepancy. Methods: We conducted a prospective multicenter molecular epidemiology study (JME study; Kawaguchi T, J Clin Oncol 2016), collecting 680 surgically resected AD cases including 335 major EGFR mutated cases (N = 263 for stage I, N = 39 for stage II, N = 33 for stage III and IV) and examining somatic mutations in 72 cancer-associated genes using targeted deep sequencing. We sought to examine whether EGFR mutational subtypes (exon 19 / exon 21) and other factors could be associated with co-mutations using the database from the JME. Results: There were 147 cases in del19 group and 188 cases in L858R group, which had 36 / 44 male, 31 / 43 smokers (median 34 / 34 pack years) with a median age of 68 / 69-year-old, respectively. The frequency of co-mutations was 29.9% and 29.3% respectively, indicating no significant difference between the two EGFR subtypes. In advanced cases with stage III and IV, L858R group had more co-mutations than del19 group (60.0% vs. 53.8%). The genotypes of co-mutations detected in del19 and L858R were TP53 (16.3% and 19.6%), CTNNB1 (3.4% and 4.3%), and PIK3CA (2.7% and 3.2%), respectively. Aside from EGFR mutations, other clinical factors were also examined, and univariate analysis showed that the frequency of co-mutations was significantly higher in gender male (p < 0.05) and pathological stage more than stage I (p < 0.01). In a logistic regression analysis, male (OR = 2.05, 95%CI: 1.01-4.14, p < 0.05) and more advanced stage (stage II-IV vs. I, OR = 3.98, 95%CI: 2.26-7.01, p < 0.01) were significantly associated with more co-mutations, considering age ( < 65 years / ≥65 years), smoking history ( < 30 pack-years / ≥30 pack-years) and EGFR subtypes. Conclusions: There was no difference in co-mutation status between the two EGFR subtypes in surgically resected lung AD. Cases in advanced stage or male cases had more co-mutations, with consideration of age, smoking history and EGFR subtypes.
Ki67 as a prognostic factor in low grade serous ovarian cancer (LGSOC): A retrospective analysis of the Tumor Bank Ovarian Cancer (TOC).
Authors: Jalid Sehouli, Helmut Plett, Rolf Richter, Carsten Denkert, Silvia Darb-Esfahani, Radoslav Chekerov, Wolfgang D Schmitt, J.P. Grabowski, Eliane T Taube, Elena Ioana Braicu
Journal: Journal of Clinical Oncology (2017)

5562 Background: LGSOC is a rare and distinct entity characterized by younger age, lower response to chemotherapy and better clinical outcome. Aim of this study was to evaluate the impact of Ki67, estrogen and progesterone receptors (ER and PR) on platinum response and survival in primary LGSOC patients. Methods: 80 primary LGSOC patients with available FFPEs were identified within TOC. The histology was confirmed at a second histological evaluation. For Ki67 analysis conventional immunohistochemical staining was performed with the Mib-1 clone on Ventana. Slides were explored with a light microscope camera. A representative field for Ki-67 evaluation was selected, in case of heterogeneous staining a hot spot was chosen. The software classified detected cells into non-tumor, negative and positive cells. When necessary, a correction of tumor and non-tumor areas was performed by an experienced pathologist. The counted cells ranged between 175 and 2398. Overall the method allows a precise, continuous and standardized means to quantify Ki-67. ER and PR status was determined on scanned IHC TMA slides. ER and PR positive tumors were defined if the percentage of stained tumor cells was at least 10%. Statistical analysis was performed using IBM SPSS Statistics. Results: Median age at diagnosis was 56 years (range: 20-81), 81.3% of patients presented in advanced stage and 96.3% received platinum based chemotherapy. Ki67 median value was 5.09 (IQR: 1.56-10.5). 93.1% and 47.9% of the patients showed ER and PR positive tumors, respectively. Median overall survival (OS) was 45.5 months (range: 0.1-182.8). Our analysis showed that platinum free interval (PFI) was significant longer in patients with lower Ki67 (p = 0.006). Higher proliferation rates were significant associated with poorer progression free (p = 0.011, HR = 1.039, 95%CI: 1.009-1.070) and OS rates (p = 0.001, HR = 1.059, 95%CI: 1.025-1.095). No differences in clinical outcome were seen in patients with different ER and PR status. Conclusions: This is the first study showing that higher Ki67 values correlate with shorter PFI and poorer survival rates in LGSOC, underlying the heterogeneous character of this disease.
P01.117 Differentiating high grade gliomas with CT based radiomics
Authors: I Compter, M Verduin, H C Woodruff, R T H Leijenaar, A A Postma, A Hoeben, D B P Eekers, P Lambin
Journal: Neuro-Oncology (2018)

Radiomics is the high-throughput extraction of large amounts of image features from radiographic images, which allows capturing the tumour phenotype in a 3D and non-invasive way. It can have an important role in predicting clinical outcome and has the potential to support personalized medicine for different types of cancer. Despite of its lower soft tissue contrast compared to MRI, the value of CT radiomics has already been demonstrated for various tumor types. In this study we assess the diagnostic power of CT radiomics when correlated with tumor grade determined by pathology in high grade glioma (WHO grade III and IV). Clinical data and pre-treatment CT images were obtained from 127 patients with either an anaplastic astrocytoma (WHO gr III) or glioblastoma (WHO gr. IV), diagnosed with a biopsy only and treated with radiotherapy +/- temozolomide between 2004 and 2015 at our institute. The tumour volume was manually delineated by an expert for radiotherapy planning purposes on MRI, coregistered with CT. In total, ~1300 radiomic features were extracted, comprising of: a) first-order statistics, b) shape, and c) (multiscale) texture. After removing highly correlated features and performing recursive feature selection, the 10 most relevant features were used to construct a random forest classification model. A ROC-curve was plotted in order to assess the discriminative power of the model for overall survival independent of clinical characteristics. The cohort was split into two groups based on the median of the established model. The model resulted in a cross-validated AUC of 0.91 (95% CI: 0.87 - 0.94). The points on the calibration plot were all close to the diagonal line indicating a well-calibrated model. A median split of patients based on the model predictions resulted in a significantly different median overall survival (p < 0.001). Results were internally validated through randomisation of outcomes when constructing the model, which yielded an AUC of 0.5 (95% CI 0.44 - 0.59), indicating that the model is not overfitted. A Schoenfeld test demonstrated that the assumption of the proportional hazard (Cox) holds true. Radiomics on pre-treatment CT-images can predict tumour grade, which may be specifically valuable for patients ineligible for a biopsy or resection. It has the potential to identify molecular subgroups which can support personalized treatment for glioma. The results will also be validated in two large independent datasets (n ~ 210) which will be presented at the EANO 2018 meeting. Additionally the dataset will be expanded to include both MR imaging and genomic profiling.
Evaluation of cardiovascular status in clinical trials in breast cancer.
Authors: Ohad Oren, Michal Oren
Journal: Journal of Clinical Oncology (2017)

e14038 Background: With the expansion of treatment options in oncology, patients are now increasingly exposed to potentially cardio-injurious compounds. Nevertheless, many clinical trials do not assess the cardiac status of participants, from time of enrollment to study completion. Methods: We reviewed the landmark clinical trials of each of the single-agent chemotherapies specified by the NCCN for use in locally advanced/metastatic breast cancer. We analysed the cardiovascular exclusion criteria, baseline cardiac evaluation as well as cardiac surveillance of patients in each study. We then investigated the literature in the years following each index publication, scrutinising for evidence of cardiac toxicity. Results: 14 phase 2/3 studies were analysed. The total number of patients was 2,522. 42.8% (6/14) of the studies excluded patients with clinically-determined cardiovascular disease, 66.6% (4) of which specified normal EF as a pre-requisite for enrollment. 42.8% (6/14) of the studies evaluated the baseline cardiovascular function of participants using EKG or TTE. 35.7% (4/14) of the studies included a more rigorous monitoring that included serial EKGs and/or TTEs. New Heart Failure (HF) occurred in 1.63% (20/1226) and 0.87% (9/1024) of patients in the more- and less- rigorous trials, respectively (P value = 0.11). Subsequent follow-up studies (published a mean of 8.5 years later) disclosed significantly higher incidence of symptomatic HF (range 2.3-28.0%) with 3 (of 4) chemotherapies in the more-rigorous study group (doxorubicin, cyclophosphamide, epirubicin) and 1 (of 10) chemotherapies in the less-rigorous group (docetaxel). Conclusions: The majority of clinical studies in breast cancer do not prospectively assess cardiac status beyond a pure clinical assessment. The discrepancy between the toxicity profile shown by original studies and that detected in subsequent investigations implies that the tools currently used to evaluate the cardiovascular status of enrollees may be insufficiently sensitive in predicting the development of HF. Novel tools (circulating markers, imaging) and longer follow-up periods are needed to ascertain the cardiotoxic profile of new chemotherapies.
Cost effectiveness in a supportive care unit.
Authors: Sophie Morin, Pauline Leroy, Christophe Aubaret, Karine Legeay, Alexandre Saadi, Cloé Brami, Claire Gervais, Christian Herve, Marie-France Mamzer, Clarisse Sauvajot, Anne Guillou, Barbara Garnier, Fabrice Lecuru, Lorraine Waechter, Florian Scotte
Journal: Journal of Clinical Oncology (2017)

e18326 Background: Supportive care in cancer (SCC) may create a financial burden, compared to a standard cancer department. In 2011, a specific SCC inpatient unit was developed in an academic hospital, based on a multidisciplinary approach in order to anticipate patient’s disability and limit emergency hospitalization. Assess the cost effectiveness of the SCC unit expenses and benefits compared to Medical (MO) and Gastro-Intestinal (GI) oncology departments. Methods: Data were analyzed over a six year period (2011-2016). Cost of hospital stays and cost per year were calculated based on the hospital’s standard cost accounting method. Hospital benefits were calculated as the difference between total incomes and total expenses (cost and Diagnosis Related Group tariffs for the stay) and results were compared (period available for comparison 2011 to 2014). Results: Total costs for the hospital, primarily due to staff expenses, were lower for the SCC unit compared to MO and GI in 2011 and 2014, as well as the daily cost per stay (DCS). Benefit per year was also higher for the SCC unit permitting it, to benefit financially compared to the two other oncology units (Table). Incomes reimbursed by the National Health system for SCC unit were 1,632,601 euros in 2015 and 2,096,285 euros in 2016 with a total of 357 and 408 patients admitted in the 8 bed SCC unit in 2015 and 2016 respectively. Conclusions: The SCC unit was less expensive to operate compared to our other oncology units. Our results suggest that its development permitted the oncology department to enhance its quality of care without any additional expenses. [Table: see text]
Pilot study of first-in-class antimitochondrial metabolism agent, CPI-613, as salvage monotherapy for small cell lung cancer.
Authors: Thomas Lycan, Timothy S. Pardee, William J. Petty, Ralph D'Agostino, Marcelo Raul Bonomi, Antonius Arthur Miller, Michael Chan, Jimmy Ruiz
Journal: Journal of Clinical Oncology (2016)

e20100 Background: Small cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80% but with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells. Methods: We evaluated CPI-613 with a single-arm, open-label phase II study in patients with relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and 4 of weeks 1-3 of 4 week cycle. Two cycles were given to complete a treatment course prior to re-evaluation. The primary outcome was response rate as assessed by CT imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and toxicity. Twelve patients were accrued (median age 57yo) who had previously received between 1 and 4 lines of chemotherapy (median 1) for SCLC with a treatment-free interval of less than 60 days in 9 of the 12 patients. They received a total of 16.3 cycles (median 1.63) of therapy with a median maximum CPI-613 dosage of 30,000 mg/m2 (range 9,000 to 36,000). Results: No complete or partial responses were seen. Ten patients (83%) progressed as best response and 2 (17%) were not evaluable for response. Median time to progression was 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall survival of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack of efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequently treated with standard topotecan then demonstrated treatment response with survival for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synergy in-vitro for CPI-613 with topotecan. Conclusions: Single agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combination with a topoisomerase inhibitor is warranted. Clinical trial information: NCT01931787.
TCT-653 Acute/mid-term results of Drug Coated Balloon following Rotational Atherectomy
Authors: Taito Nagai, Takashi Nishiura, Shojiro Hirano, Junpei Koike, Yoshihiro Iwasaki, Tomonori Takahashi, Satoshi Tokimasa, Ritsu Yoshida, Masahiro Mizobuchi, Atsushi Funatsu, Kobayashi Tomoko, Shigeru Nakamura
Journal: Journal of the American College of Cardiology (2018)
Potential effect of household contact management on childhood tuberculosis: a mathematical modelling study
Authors: Peter J Dodd, Courtney M Yuen, Mercedes C Becerra, Paul Revill, Helen E Jenkins, James A Seddon
Journal: The Lancet Global Health (2018)

BackgroundTuberculosis is recognised as a major cause of morbidity and mortality in children, with most cases in children going undiagnosed and resulting in poor outcomes. Household contact management, which aims to identify children with active tuberculosis and to provide preventive therapy for those with HIV or those younger than 5 years, has long been recommended but has very poor coverage globally. New guidelines include widespread provision of preventive therapy to children with a positive tuberculin skin test (TST) who are older than 5 years.MethodsIn this mathematical modelling study, we provide the first global and national estimates of the impact of moving from zero to full coverage of household contact management (with and without preventive therapy for TST-positive children older than 5 years). We assembled data on tuberculosis notifications, household structure, household contact co-prevalence of tuberculosis disease and infection, the efficacy of preventive therapy, and the natural history of childhood tuberculosis. We used a model to estimate households visited, children screened, and treatment courses given for active and latent tuberculosis. We calculated the numbers of tuberculosis cases, deaths, and life-years lost because of tuberculosis for each intervention scenario and country.FindingsWe estimated that full implementation of household contact management would prevent 159 500 (75% uncertainty interval [UI] 147 000–170 900) cases of tuberculosis and 108 400 (75% UI 98 800–116 700) deaths in children younger than 15 years (representing the loss of 7 305 000 [75% UI 6 663 000–7 874 000] life-years). We estimated that preventing one child death from tuberculosis would require visiting 48 households, screening 77 children, giving 48 preventive therapy courses, and giving two tuberculosis treatments versus no household contact management.InterpretationHousehold contact management could substantially reduce childhood disease and death caused by tuberculosis globally. Funding and research to optimise its implementation should be prioritised.FundingUK Medical Research Council, US National Institutes of Health, Fulbright Commission, Janssen Global Public Health.