tbuckley/cabot-search huggingface dataset:
Addressing survivorship challenges using a collective impact approach.
Authors: Patti Migliore Santiago, Rose Guerrero, Chinmaya Rajderkar, Carol Vanevenhoven
Journal: Journal of Clinical Oncology (2017)

64 Background: The American Cancer Society (ACS) estimates 352,830 cancer survivors in WA State today. We had a group of avid stakeholders in the WA CARES About Cancer Partnership wanting to address survivorship issues. The challenge was how to work together to focus on improving the quality of life beyond treatment, recognizing that no single organization has the ability to solve the issues alone. Individual organizations were going their own way creating a duplication of effort. What would it look like if we aligned resources? We had influential champions, grant funds, and a true sense of urgency for change. Methods: We turned to FSG and their research on collective impact. Phase 1 of a collective impact approach was completed. We formed a cross-sector group, mapped the cancer survivorship landscape utilizing state cancer registry data, ACS Survivorship Report and local facility input. In Phase 2 a common agenda was agreed upon. Shared measurements of success for Survivorship Care Plans (SCP) were set. Mutually reinforcing activities were developed in an action plan. Methods and frequency of communication were decided. WA Dept. of Health (DOH) was designated as the hub organization. Results: DOH provides adaptive leadership skills and the ability to mobilize people without imposing an agenda or taking credit for success. We hosted a GW Cancer Institute Executive Training on Survivorship, June 2015. We held a 2 day planning retreat to develop a common agenda and action plan, Dec. 2015. Developed and deployed survey for CoC accredited hospitals to create a baseline for SCP utilization and challenges, Feb. 2016. In May 2016 we hosted 1 day retreat for the leadership team to finalize its action plan and added a second priority to launch a pilot in Yakima County to partner with 2-1-1 to provide resources to survivors. We have moved from having uncoordinated plans to embracing a centralized system. Conclusions: We recognize the need to identify and catalog previously unnoticed resources and make them available statewide; perform ongoing evaluations to elicit feedback for decision making; and, the need for further study to determine if tailored SCP and 211 resources improve patient/provider survivorship experience and attain financial sustainability.
Volumetric changes of the primary esophageal tumor during radiation therapy.
Authors: Brady Laughlin, Justin Famoso, John Gloss, Joseph Frankl, Emad Elquza, Krisha Howell
Journal: Journal of Clinical Oncology (2017)

134 Background: Management of esophageal cancer with radiotherapy requires weeks of daily treatments. The objective of this study is to identify edematous/obstructive changes in the esophageal tumor occurring during therapy and quantifying its change relative to the original tumor volume. Methods: A total of 66 patients were reviewed on a retrospective IRB-approved protocol between July 2012 – July 2016. The gross tumor volume (GTV) targeted with radiation (GTV sim ) was constructed on a CT-simulation image. Cone beam CT images (CBCTs) were taken daily during treatment. GTVs (GTV CT# ) were contoured on the CBCT on treatment days 1, 6, 11, 16, 21, and 25. Volumes for the GTV sim and each GTV CT# per patient were calculated. A conformality index (CI) was determined by visual confirmation of overlap and calculation of GTV CT# /GTV sim . The standard deviation (SD) was calculated. A theoretical max volume (GTV CTMAX ) was determined per patient based on the upper range of 2SD from the average GTV CT# value. A theoretical PTV created from a 1cm (PTV 1 ) and 0.5cm (PTV 0.5 ) expansions were also calculated with associated CIs for PTV CTMAX /PTV 1 and PTV CTMAX /PTV 0.5 . Results: Twenty-one patients had a total of 94 CBCT volumes. The median age was 67 years (53-83), sixteen patients were male, 5 female. T-stage was 1/2 in 5 patients and 3/4 in 15 patients. Chemotherapy was administered concurrently in 17 patients. Median duration of radiotherapy was 35 days (2-50). Results were analyzed by absolute volume comparison and CI calculations as noted in table 1.The median CI for PTV CTMAX /PTV 1 was 0.40 (0.15-0.84) and PTV CTMAX /PTV 0.5 was 0.65 (0.34-0.89). Conclusions: Review of the weekly CBCTs demonstrated a larger tumor volume in the first day of therapy relative to the subsequent weeks, and even relative to the volume at the time of simulation. However, in projecting potential changes in maximum size of the individual tumors, 100% remained within standard PTV volumes constructed with a 1cm and 0.5cm expansions. [Table: see text]
Design and implementation of an informatics infrastructure for actionable precision oncology.
Authors: Jonathan Hirsch, James M. Ford, Lincoln Nadauld, Andro Hsu
Journal: Journal of Clinical Oncology (2015)

e17521 Background: Precision medicine has the potential to revolutionize cancer care by matching the right patient to the right therapy. Using genomics in routine care to guide therapy selection requires decision-support tools to deliver simple guidance based on complex data in real-time in the clinical workflow. Electronic health records do not support precision medicine, and critical data remains siloed in non-searchable systems. Methods: Syapse has created a precision medicine data platform, aggregating and structuring clinical, genomics, and outcomes data using semantic computing. Traditional clinical data, such as treatment, pathology, and radiology are extracted from clinical data systems such as EHRs. Genomic and molecular data are ingested using lab data connectors. Knowledge, such as variant annotation and guidelines, is entered as structured data by oncology experts. A user interface enables oncologists to view an integrative profile of their patient, access decision support for treatment planning, act on guidance by ordering tests, procuring therapies, or requesting enrollment in a trial, and track outcomes longitudinally. Oncologists can query patient cohorts for clinically similar patients and view treatments and outcomes, enabling real-time comparative effectiveness. Results: Stanford and Intermountain have implemented the platform to support precision medicine. Over 10 siloed data systems must be integrated using a custom-created ontology containing over 2000 concepts. EHR workflow integration was not necessary for physicians who routinely used genomics prior to software implementation, but was necessary for physicians who were new to use of genomics. Decision support for genomic testing increased test volumes. Decision support therapy selection based on genomics resulted in an increased rate of prescription of molecularly-targeted therapies. Results of change of physician decisions and patient outcomes will be presented by Intermountain at this conference. Conclusions: Implementation of a precision medicine program is achievable today. An informatics infrastructure that enables clinical genomics decision support results in increase adoption of precision medicine.
Predictive value of gene expression signatures in premalignant lesions of the head and neck for response to chemoprevention with EGFR and COX-2 inhibitors.
Authors: Nabil F. Saba, Michael R. Rossi, Bhakti Dwivedi, Jeffrey M. Switchenko, Kelly R. Magliocca, Suresh S. Ramalingam, Taofeek Kunle Owonikoko, Fadlo Raja Khuri, Zhuo Georgia Chen, Jeanne Kowalski, Dong Moon Shin
Journal: Journal of Clinical Oncology (2014)

e17053 Background: Epidermal growth factor receptor (EGFR) and cyclooxygenase 2 inhibitors synergistically inhibit head and neck squamous cell carcinoma (HNSCC) tumorigenesis in preclinical studies. We explored the presence of a genomic signature that can predict outcome in patients with pre-malignant lesions using expression data by the nCOunter nanoString platform. Methods: We employed a 236 cancer gene panel by nCounter nanoString to compare the baseline and post therapy samples from two patients treated with celecoxib and erlotinib on a phase I chemoprevention trial: a responder (severe dysplasia at baseline reduced to mild dysplasia 3 months after treatment, with no diagnosis of HNSCC as of 1 year after treatment) and non-responder (moderate dysplasia at baseline and 3 months after treatment, with diagnosis of HNSCC as of 1 year after treatment). We examined the association in expression among a subset of 28 genes, between samples obtained from a biopsy versus cytobrush, at baseline for each of the two patients. Results: Profiles at baseline and 3 months post treatment showed differential increased expression of CDC2, ATM, NTRK3, BRCA2 and IFGBP6 gene in the responder, but significant decrease in the non-responder. A reverse pattern of decreased expression in the responder and increased expression in the non responder was noted for NOTCH1, TFGB, ETS1, FGFR1, HCK, CDH1, and TNSF10. Among the 28 gene subset a significant, positive correlation was observed between biopsied and cytobrush specimens at baseline, for the responder (r=0.454; p-value=0.015) and the non-responder (r=0.52; p-value=0.004). Conclusions: Although preliminary, our results highlight potential biomarkers of expression that characterize a responder distinct from a non-responder in patients with pre-malignant lesions of the head and neck and provide evidence of an association in expression between the use of biopsy and cytobrush samples using nanoString technology. Findings from this analysis highlight the potential value of gene expression profiling as a predictive tool for assessing response in chemoprevention trials. (This work was supported in part by a U01 101244 grant to DMS)
Hodges’ Frontotemporal Dementia, Second Editionedited by Bradford C. Dickerson, M.D. New York, Cambridge University Press, 2016, 311 pp., $135.00 (hardcover).
Authors: Sheldon Benjamin, Joseph M. Keating
Journal: American Journal of Psychiatry (2017)

psychodynamic approach, environmental influence, the relevance of individual development, and the doctor-patient relationship, and his two long case histories are of potential use to many clinicians.
Randomized, open-label trial evaluating the preventive effect of tetracycline on afatinib induced-skin toxicity in non-small cell lung cancer patients.
Authors: Oscar Arrieta, Maria Teresa Vega-Gonzalez, Diego Lopez-Macias, Omar Macedo, Ludwing Bacon Fonseca, Diana Flores Estrada
Journal: Journal of Clinical Oncology (2014)

8094 Background: Afatinib has shown high objective response rates and prolonged progression-free survival in patients with metastatic non-small cell lung cancer (NSCLC). The most common toxicity of this agent is acneiform rash, which may have a negative impact on quality of life. Tetracyclines are used as treatment for this adverse event (AE). No randomized trial have evaluated the prophylactic efficacy treatment of tetracycline in afatinib induced-skin toxicity. Methods: We performed an open-label, randomized, controlled trial to assess the preventive effect of tetracycline for reducing afatinib skin toxicity. Patients receiving afatinib treatment (40mg/day) were randomly assigned to pre-emptive or reactive treatment (after skin toxicity developed). Pre-emptive comprised tetracycline 250 mg/d for 4 weeks and reactive treatment included the use of skin moistures, sunscreen, topical steroids and tetracycline according to the severity of toxicity. All patients were blindly monitored for rash and other adverse events at baseline, 2 weeks and 4 weeks. Cutaneous toxicity was reported according to the Common Terminology Criteria for Adverse Events v4.0 (CTCAE). The protocol is registered on ClinicalTriasl.gov with the number NCT01880515 Results: We included 90 patients. No differences were found in clinical and dermatological baseline characteristics. The incidence of adverse events of any grade and grade ≥2 were lesser in the pre-emptive arm versus the control arm (55.6 vs. 75.6%, RR 0.4 [95% CI 0.17-0.99, p=0.046 and 15.6 vs. 35.6%, RR 0.35 [0.12-0.91], p=0.030; respectively). No difference was found in other dermatologic adverse events like paronychia, xerosis, mucositis, folliculitis and skin fissure. Nor the presence of rash or pre-emptive treatment with tetracycline impact on response rate, progression-free survival and overall survival. No adverse events were associated with tetracycline. Conclusions: The incidence and severity of rash associated with afatinib was reduced by 60% in the tetracycline group compared with the control group. Its use can positively impact quality of life in patients who are candidates for afatinib treatment. Clinical trial information: NCT01880515.
Uncertainty around individualized predictions using nomograms: The concept of individualized prediction intervals
Authors: A. Iasonos, D. Schrag, G. V. Raj, P. Russo, K. S. Panageas
Journal: Journal of Clinical Oncology (2007)

6526 Background: Nomograms have become popular in the clinical oncology community, because of their simplicity. Clinicians use nomograms to provide individualized prognostic estimates to patients based on their clinical and pathologic characteristics.We aim to evaluate the degree of uncertainty around individualized point estimates derived from a published nomogram. Methods: Predictions were evaluated from a published nomogram (Raj G.V et al, J Urol. 2007;177(1):53–8.), where the predicted outcome was clear cell (CC) histology in renal masses using pre-operative parameters.95% confidence intervals (CI) for each prediction were obtained from logistic regression using the SAS system.CIs depend on the covariate effect in the underlying model and the patient-specific values of the covariates, hence they differ from patient to patient.The width of the CI was used to assess the zone of uncertainty of the predictions for each individual patient in this cohort. Results: Predictions were obtained for each of the 299 patients in the cohort. The median width of the 95% CI around the point estimates was 18% (range 11–47%) indicating that 50% (147/299) of patients have ± 9% uncertainty and 95% (283/299) of patients have less than ±16% uncertainty around the estimate predicted by the nomogram. Only three patients (1%) have more than ±20% uncertainty around the nomogram derived estimate. For example, a 69-year-old male with a 3.9 cm renal mass, without vascular flow on Doppler ultrasound, has 18% probability of CC histology with 95% CI: 10–29%, whereas a 48-year-old female with 9.7cm renal mass without vascular flow has 18% probability of CC histology with 95% CI:7–41%. Conclusions: We demonstrate that patients with equal predicted probability from a nomogram may have different uncertainty around their prediction. When nomograms are used to convey prognostic information to patients, reporting strategies should incorporate the degree of uncertainty around the point estimates that are derived from the underlying regression models.Although, this strategy adds some degree of complexity to the graphical representation of results, it enhances the integrity of the exercise and conveys to patients the important message that uncertainty is inherent in prognostication. No significant financial relationships to disclose.
Abstract P206: Coffee Intake Was Not Causally Associated With Type 2 Diabetes Risk in Asians: a Mendelian Randomization Based on the Singapore Chinese Health Study
Authors: Mohammad Talaei Pashiri, Tao Huang, Woon-Puay Koh
Journal: Circulation (2017)

Introduction: Despite the largely reported inverse association between coffee intake and type 2 diabetes (T2D) risk by observational studies, the causality of such association is not well established. Hypothesis: We assessed the hypothesis that the observationally inverse association between coffee intake and T2D risk is causal. Methods: In a nested case-control study within the Singapore Chinese Health Study cohort, we included 2436 T2D cases and 2436 matched controls. At biospecimen collections (1999-2004), participants were free of diagnosed T2D, cardiovascular disease and cancer. Cases were participants who reported to have physician-diagnosed T2D at follow-up visits during 2006-2010. Controls were randomly selected among those who remained free of T2D and were matched to the index cases by age, sex, dialect group and date of biospecimen collection. We 1) tested the association between coffee intake and T2D risk using conditional logistic regression analysis; 2) tested the association of the nine single-nucleotide polymorphisms (SNPs) with coffee intake or risk of T2D; 3) used the instrumental variable (IV) estimators to quantify the strength of the causal association of coffee intake and risk of T2D. The IV estimator (β IV ) which is identical to that derived by the widely used two-stage least squares method, was calculated through dividing the β of the regression coefficients for SNP-T2D by SNP-coffee associations. Results: Median intake (inter quartile range) for coffee intake was 1.00 (0.36-2.51) cups/day in this population. Coffee intake was observationally associated with lower risk of T2D and OR (95% CI) was 0.93 (0.88-0.98) in multivariate adjusted model. We found three SNPs that were significantly associated with higher coffee intake with β coefficients (95% CI) as follows: 0.73 (0.23, 1.24) for rs4410790 (P=0.004), 0.72 (0.22, 1.22) for rs6968554 (P=0.005), and 1.60 (0.28, 2.91) for rs7800944 (P=0.017). Among these tree SNPs, two SNPs were marginally associated with higher T2D risk with OR (95% CI) identically 1.08 (0.99, 1.18) for 7:17284577 and 7:17287106, and the other one was insignificantly associated with lower risk (OR 0.94; 95% CI 0.75, 1.18). The estimated β IV coefficients (95% CI) was not statistically significant for any of the three SNPs: 0.10 (-0.04, 0.25) for rs4410790 (P=0.16), 0.11 (-0.04, 0.25) for rs6968554 (P=0.15), and -0.04 (-0.19, 0.11) for rs7800944 (P=0.60). Conclusions: High coffee intake was observationally associated with lower T2D risk, but our finding does not support a causal association.
Changing prognosis of metastatic colorectal adenocarcinoma (mCRC) 1988-2008 within the general population: Has everyone benefitted?
Authors: Yaacov Richard Lawrence, Talia Golan, Dan Aderka, Adi Shani, Leor Zach, Merav A. Ben-David, Iris Gluck, Tatiana Rabin, Raphael M. Pfeffer, Raphael Catane, Raanan Berger, Zvi Symon
Journal: Journal of Clinical Oncology (2012)

e14143 Background: Between 1991 and 2008 the FDA approved 7 new drugs for the treatment of mCRC. The results of randomized phase III trials, performed on selected (e.g. younger) patient populations, may not reflect net benefit seen within the general population. We therefore performed a population-based survival analysis of patients who initially presented with mCRC. Methods: Survival statistics were extracted from the Survival, Epidemiology and End Results (SEER) Database for patients diagnosed with mCRC between 1988-2008. Survival was analyzed using the Kaplan-Meier method and proportional hazard models as appropriate. Exclusion criteria included diagnosis at autopsy, non-adenocarcinoma and unknown histology. Results: The study population consisted of 42,347 patients diagnosed with mCRC from 1988-2008, 52% female. Mean age 67 years; 46% were aged 70 or over. Prognostic variables included race, gender, age, marital status, disease site, surgical resection and year of diagnosis (for all p&lt;0.001). For the entire population median OS improved from 8 months in 1988 to 14 months in 2007. Net improvement in OS was highly dependant upon age: for pts&lt;50 yr OS improved from 9m to 21m; for pts 50-69 yr from 10m to 17m; for pts &gt;=70 yr from 7 to 8m. Conclusions: There has been a continuous improvement in OS of patients diagnosed with mCRC between 1988 and 2008. We could not determine if this was due to new therapeutic agents or improved imaging leading to earlier diagnosis. Little improvement has been seen in patients &gt;70 years age. The disparity in median OS between younger and older patients with mCRC over this period has widened from 2 months in 1988 to 13 months in 2008.
Regarding Twitter as a Potential Data Source for Cardiovascular Disease Research—Reply
Authors: Lauren Sinnenberg, David A. Asch, Raina M. Merchant
Journal: JAMA Cardiology (2017)

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