tbuckley/cabot-search huggingface dataset:
Clinical documentation improvement as a quality metric in oncology.
Authors: Jeffrey Ian Farber, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2014)

123 Background: With the rapid pace of healthcare reimbursement transformation from a fee-for-service to a fee-for-value system, clinical documentation is increasingly recognized as a critical area of focus for quality improvement. Engaging busy physicians to improve their clinical documentation is a challenging endeavor. Many hospitals utilize clinical documentation improvement specialists to query physicians for more specific and comprehensive clinical documentation. In this paper, we will report on a novel, complementary, and replicable approach we utilized to improve clinical documentation in the medical oncology clinical service line at the Mount Sinai Hospital in New York City. Methods: We organized a team of stakeholder physicians, clinical documentation specialists, clinical informaticists, and data analysts in July 2013 to address a perceived gap in publicly-reported severity-adjusted quality metrics in medical oncology. We used University Health System Consortium data to conduct a detailed comparative analysis of the rates of coding for common and important secondary ICD-9 diagnoses on inpatient claims by base Diagnosis Related Group (DRG). A list of 34 diagnoses was targeted for improvement in the accuracy and specificity of clinical documentation. We then developed an electronic medical record tool to assist clinicians in real-time clinical documentation. We rolled out a new quality metric with monthly reporting on CC/MCC (complication or comorbidity and major complication or comorbidity) capture rates to departmental leadership, provided educational outreach to front-line providers and developed additional non-electronic reminder tools for provider use. Results: We increased the overall CC/MCC capture rate from 88% to 94% and the case mix index (CMI) for the chemotherapy base MS-DRG from 1.11 to 1.28 from March 2013 to March 2014. The capture rate remained the same (6) or increased (18) in 82% of the targeted diagnoses. Conclusions: Adding clinical documentation metrics to the existing quality infrastructure, supported with comparative analytical data and EMR tools, can drive sustainable improvements in clinical documentation which supports publicly-reported severity-adjusted quality measures.
Induction of endothelial proliferation and angiogenesis through activating the ERK1/2/EGF pathway mediate by CXC chemokine receptor 2 by chemokine (C-X-C motif) ligand 1.
Authors: Makito Miyake, Steve Goodison, Evan Gomes, Wasia Rizwani, Shanti Ross, Ge Zhang, Charles Joel Rosser
Journal: Journal of Clinical Oncology (2013)

138 Background: Endothelial cell growth and proliferation are critical for tumoral angiogenesis. We report here that blockade of Chemokine (C-X-C motif) ligand 1 (CXCL1) results in reduction of human endothelial cell proliferation and its ability to induce angiogenesis. Methods: Two human endothelial cell lines, HUVEC and HDMEC, were used in the in vitro assays. Proliferation assay and matrigel tube formation assay were performed to test the inhibitory effect of anti-CXCL antibody on the activity of endothelial cells in vitro. Matrigel plug assay in nude mice was performed to test the in vivo angiogenic activity of CXCL1. Results: CXCL1 interacts with its receptor CXC chemokine Receptor 2 and induces endothelial cell proliferation, whereas blockade of CXCL1 is associated with reduction in cellular proliferation through a decrease in levels of cyclin D and cdk4 and inhibition of angiogenesis through EGF and ERK 1/2. Targeting CXCL1 inhibits neoangiogenesis but has no effect on disrupting established vasculature. Furthermore targeting CXCL1 is associated with reduction in migration of human endothelial cells in an in vitro model. Additionally, neutralizing antibody against CXCL1 in a xenograft angiogenesis model resulted in inhibition of angiogenesis. Conclusions: CXCL1-induced regulation of angiogenesis has not been studied extensively in human cancers, thus these findings illustrate a novel contribution of CXCL1 interactions in pathological angiogenesis. Therefore, the ability to selectively modulate CXCL1, specifically in tumoral angiogenesis, may promote the development of novel oncologic therapeutic strategies.
FGFR2 expression to predict survival outcome in patients with metastatic papillary renal cell carcinoma.
Authors: Ilya Tsimafeyeu, Alexandra Naumova, Evgenia Stepanova, Alfia Khasanova, Ilya Varlamov, Nigel Wynn, Anton Snegovoy, Lev V. Demidov
Journal: Journal of Clinical Oncology (2016)

506 Background: In our previous study we showed that fibroblast growth factor receptor 2 (FGFR2) mutations are rare across papillary types of renal cell carcinoma (pRCC). The aim of the present study is to test FGFR2 expression for association with survival outcome in the largest patient cohort to date. Methods: Formalin-fixed, paraffin-embedded specimens of removed primary tumors from 214 untreated metastatic pRCC patients were evaluated by immunohistochemistry with FGFR2 antibody (Santa Cruz Biotechnology). Expression was quantified by consensus of two independent observers using a four-value intensity score (0, 1+, 2+, and 3+) and the percentage (0-100%) of the extent of reactivity. Expression was scored according to the percentage of positive cells present among all tumor cells in the section. The cytoplasmic and nuclear expression score was obtained by multiplying the intensity and reactivity extension values (range, 0-300). FGFR2 expression was tested for associations with progression-free survival (PFS), overall survival (OS) and best objective response. Results: Expression of FGFR2 was observed in 23% (49/214) of primary pRCC, mostly in cytoplasm of tumor cells. 2 of 214 (1%) patients had nuclear FGFR2 expression. Intensity was 3+ in all cases. Expression of FGFR2 was significant lower in the normal tissue of kidney (1%, P=0.001). FGFR2 expression was strongly associated with a number of metastatic sites (2 and more metastatic sites vs. 0-1), type 2 of pRCC, lower nucleolar grade (P&lt;0.001). FGFR2-positive patients had significantly shorter OS and PFS in first-line therapy (P&lt;0.05; Table). On multivariate analysis, FGFR2 expression, MSKCC risk group, and type of pRCC were found to be independent predictors of survival. Conclusions: In this study, we described immunohistochemical expression of FGFR2 in a large series of pRCC specimens. FGFR2 expression was found to be prognostic factor for survival in patients with metastatic pRCC. Clinical trial information: rosoncoweb2011. [Table: see text]
Integrative medicine modality utilization and impact on quality of life in cancer patients: A single academic cancer center experience.
Authors: Denise Millstine, Krisstina L. Gowin, Tony Chon
Journal: Journal of Clinical Oncology (2016)

169 Background: The majority of patients with cancer incorporate integrative medicine strategies into their cancer experience however; patient reported preferences and impact on quality of life is limited. We present cancer patient utilization for specific integrative medicine modalities within the Mayo Clinic Arizona Comprehensive Cancer center and describe the patient perceived impact on quality of life. Methods: Patients and family members attending the 2015 Living with Cancer Symposium at Mayo Clinic Arizona completed a survey indicating whether specific integrative medicine modalities were utilized during cancer treatment and whether utilization had an impact on the patients perceived quality of life. Patient diagnoses and stage were collected. A total of 119 patient surveys were completed and analyzed. Results: The patient diagnoses included hematologic malignancies (27%), breast (25%), prostate (18%), and other (30%). Disease stage was nearly evenly distributed with stage I (21%), stage II (20%), stage III (16%), stage IV (15%), and unknown (28%). The most commonly utilized integrative modalities included nutrition (54%), natural product supplementation (34%), massage (33%), exercise (31%) including yoga (23%) and tai chi (1%), breathing and meditation interventions (26-28%), support groups (23%), and pet therapy (17%). The majority of patients (64%) reported integrative intervention utilization led to an enhanced quality of life during cancer therapy. Conclusions: At a single academic cancer center, in a cancer type and stage diverse population, the majority of patients (64%) reported improved quality of life during cancer therapy with integrative medicine intervention utilization. Nutrition, natural product supplementation, massage, exercise, and meditative modalities were most commonly utilized. Interestingly, a large proportion of patients analyzed in this questionnaire-based study were afflicted with hematologic disease, a population underrepresented in the current integrative medicine intervention research. More studies exploring the feasibility and impact of integrative therapies in the hematologic patient population are needed.
Antioxidant supplement use after diagnosis and breast cancer outcomes.
Authors: H. Greenlee, M. L. Kwan, L. Kushi, J. Song, A. Castillo, E. Weltzien, C. Quesenberry, B. J. Caan
Journal: Journal of Clinical Oncology (2011)

1539 Background: There is concern that antioxidant supplement use may decrease pro-oxidant effects of chemotherapy and radiation therapy, yet effects on recurrence and survival are largely unknown. The association of post-diagnosis antioxidant use with breast cancer (BC) recurrence and mortality was examined in the Life After Cancer Epidemiology (LACE) Study. Methods: The LACE cohort (n=2,264) consists of women identified primarily through the Kaiser Permanente Northern California Cancer Registry and diagnosed with early stage primary BC from 1997 to 2000; women enrolled approximately two years post-diagnosis. A mailed baseline questionnaire collected data on frequency of antioxidant supplement use since diagnosis (multivitamins +/- minerals, combination multiple carotenoids, beta-carotene, lycopene, vitamin C, vitamin E, selenium, zinc, coenzyme Q10, soy), and other risk factors. BC outcomes were ascertained yearly by mailed questionnaire and confirmed by chart review. Delayed entry Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Results: Antioxidant supplement use after diagnosis was reported by 81% of women; 71% used multivitamins, 40% used vitamin C, 48% used vitamin E, and 7% used combination multiple carotenoids. Among antioxidant users, frequent use of vitamin C and vitamin E were associated with decreased risk of breast cancer recurrence (HR = 0.73, 95% CI: 0.55-0.97; HR = 0.77, 95% CI: 0.54-0.94, respectively); use of vitamin E was also associated with decreased risk of all-cause mortality (HR = 0.76, 95% CI: 0.58-1.00). Conversely, frequent use of combination multiple carotenoids was associated with increased risk of death from breast cancer (HR = 2.07; 95% CI: 1.21-3.56) and all causes (HR = 1.75; 95% CI: 1.13-2.71), but no such relationship was seen with either beta-carotene or lycopene alone. Conclusions: Frequent use of vitamin C and vitamin E in the period following breast cancer diagnosis was associated with decreased likelihood of recurrence. Frequent use of combination multiple carotenoids during this same period was associated with decreased survival. Effects of antioxidant supplement use after diagnosis likely differ by type of antioxidant.
Prognostic impact of tumor-infiltrating lymphocytes (TIL's) and stromal-infiltrating lymphocytes (SIL's) in triple-negative breast cancer.
Authors: Santiago Sherwell-Cabello, Antonio Maffuz-Aziz, Diego A Camacho-Ramírez, Verónica Bautista-Piña, Nina P Ríos-Luna, Sonia Labastida-Almendaro, Sergio Rodriguez-Cuevas
Journal: Journal of Clinical Oncology (2015)

83 Background: Immune response seems to improve outcome in women with Triple-Negative Breast Cancer (TNBC). Recent data suggests that the presence of Tumor-Infiltrating Lymphocytes is an independent factor associated with better prognosis. In this study, we evaluate the prognostic impact of both TIL´s and SIL´s in patients with TNBC. Methods: Data on women diagnosed with TNBC between 2005 and 2013, was collected by retrospectively reviewing at our institute. The rate of intratumoral and/or stromal lymphocytes was evaluated in all hematoxylin and eosin-stained histopathologic sections according to Denkert et al. The five-year disease-free survival (DFS) and overall survival (OS) were compared between groups with the presence or absence of TIL´s or SIL´s. Demographic and clinical characteristics were assessed, variables with a statistical significance between groups were analyzed in a multivariate analysis. Results: A total of 172 patients with TNBC treated at this institution were included with a mean age of 49.8 years. A complete absence of tumor lymphocytes was found in 88 patients while the presence of intratumoral, stromal or both was found in 84 (48.8%). A mean follow-up of 46.12 months showed significantly higher rates of both DFS and OS in women with SIL´s and TIL´s (p = 0.014 and 0.042 respectively) in locally advanced stages (LAS), regardless the rate of infiltrating lymphocytes found [Table 1]. SIL´s are correlated with a better prognosis compared with TIL´s (p = 0.028 and 0.091 respectively). Non-significant differences were found in early stages (p= 0.255). Conclusions: These results show that the presence of SIL´s or TIL´s are strongly associated with higher rates of DFS and OS in LAS, especially when SIL´s are found, suggesting that immunity seems to play a key role regarding the outcome in women with TNBC. Independent of the rate of lymphocytic infiltrate, its presence has a statistical significance. Because it is a feasible and inexpensive test that can be used as a prognostic predictor, we suggest assessing both SIL's and TIL's in histopathologic biopsies of patients with TNBC. [Table: see text]
Restoring Cystic Fibrosis Transmembrane Conductance Regulator Function Reduces Airway Bacteria and Inflammation in People with Cystic Fibrosis and Chronic Lung Infections
Authors: Katherine B. Hisert, Sonya L. Heltshe, Christopher Pope, Peter Jorth, Xia Wu, Rachael M. Edwards, Matthew Radey, Frank J. Accurso, Daniel J. Wolter, Gordon Cooke, Ryan J. Adam, Suzanne Carter, Brenda Grogan, Janice L. Launspach, Seamas C. Donnelly, Charles G. Gallagher, James E. Bruce, David A. Stoltz, Michael J. Welsh, Lucas R. Hoffman, Edward F. McKone, Pradeep K. Singh
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Previous work indicates that ivacaftor improves cystic fibrosis transmembrane conductance regulator (CFTR) activity and lung function in people with cystic fibrosis and G551D-CFTR mutations but does not reduce density of bacteria or markers of inflammation in the airway. These findings raise the possibility that infection and inflammation may progress independently of CFTR activity once cystic fibrosis lung disease is established.Objectives: To better understand the relationship between CFTR activity, airway microbiology and inflammation, and lung function in subjects with cystic fibrosis and chronic airway infections.Methods: We studied 12 subjects with G551D-CFTR mutations and chronic airway infections before and after ivacaftor. We measured lung function, sputum bacterial content, and inflammation, and obtained chest computed tomography scans.Measurements and Main Results: Ivacaftor produced rapid decreases in sputum Pseudomonas aeruginosa density that began within 48 hours and continued in the first year of treatment. However, no subject eradicated their infecting P. aeruginosa strain, and after the first year P. aeruginosa densities rebounded. Sputum total bacterial concentrations also decreased, but less than P. aeruginosa. Sputum inflammatory measures decreased significantly in the first week of treatment and continued to decline over 2 years. Computed tomography scans obtained before and 1 year after ivacaftor treatment revealed that ivacaftor decreased airway mucous plugging.Conclusions: Ivacaftor caused marked reductions in sputum P. aeruginosa density and airway inflammation and produced modest improvements in radiographic lung disease in subjects with G551D-CFTR mutations. However, P. aeruginosa airway infection persisted. Thus, measures that control infection may be required to realize the full benefits of CFTR-targeting treatments.
Ronald Frank Fletcher
Authors: Martin Fletcher
Journal: BMJ (2017)

Ronald Frank Fletcher (“Ron”) was born in Smethwick, in the West Midlands, on 30 January, 1927. He was to live, study, and work in Birmingham for nearly his entire life. His father and elder brother were engineers, and medicine was suggested as a good alternative career.

He attended King Edward’s School and moved from the medical sixth form to Birmingham University Medical School in 1944. He took a BSc in physiology, which stimulated his interest in both academic medicine, and endocrinology. Joining the university’s mountaineering club (he was president in his last year) started his lifelong enthusiasm for hillwalking, scrambling, and …
Diagnosis of breast cancer metastases with PET/TC in patients with elevation of tumor markers: First data update.
Authors: A. Mafodda, A. Prestifilippo, D. Aricò, A. Vadalà, M. Mare, C. Fornito, D. Giuffrida
Journal: Journal of Clinical Oncology (2011)

1541 Background: Breast cancer is one of the most common cancers worldwide. PET / CT is more accurate than traditional methods for the detection of distant metastases or local recurrence and enables for early assessment of treatment response in patients after surgery for breast cancer undergoing primary chemotherapy. PET/CT is not considered a conventional examination during follow-up of patients with breast cancer, but recent data indicate its usefulness both in cases of asymptomatic increase of tumor markers that uncertain conventional imaging results. This study investigates the potential role of PET / CT to detect clinically occult metastases in patients with suspected recurrence of breast cancer during follow-up. Methods: The authors studied 51 patients in breast cancer follow-up after primary surgery and chemotherapy and/or external radiotherapy. All patients were in remission without any other clinical or instrumental signs of relapses, except for the progressive elevation of CA 15.3 and/or CEA, tested during the follow-up. In 44 patients conventional imaging provided uncertain results and increase of CA 15.3 that was not correlated to any evidence of metastatic disease. Results: Disease relapse was proven in 48 out of 51 patients and successfully PET/CT has identified clinically occult decease with an excellent sensitivity. In 21 cases the anatomical distribution of metastasis sites was in the bone, 11 in the lymphonode, 7 in the lung and 9 in the liver. Out of them we found 2 false-negative and 1 false-positive. Conclusions: PET/TC may be more sensitive than the serum tumor markers in detecting relapse of breast cancer. This study demonstrated the clinical utility of tumor marker-guided PET in the follow-up of breast cancer patients.
Profiling of a global cohort of 1,250 neuroendocrine tumors to identify multiple potential drug targets.
Authors: Igor A. Astsaturov, Steven J. Cohen, Paul F. Engstrom, Zoran Gatalica, Ryan P. Bender, Gargi Dan Basu, Sherri Z. Millis
Journal: Journal of Clinical Oncology (2014)

214 Background: Identification of new drug targets may extend treatment options for NET, regardless of histologic classification or primary organ site. Methods: 1,250 cases of infradiaphragmatic neuroendocrine tumors (all grades and sites) were identified among &gt;50,000 cases profiled in a CLIA certified laboratory. Biomarker profiling utilized multiple platforms: gene sequencing (next generation sequencing, Sanger or pyrosequencing), gene copy number by in-situ hybridization, and protein expression by immunohistochemistry. The results are shown relative to the total number of tests performed. Results: Overall, drug therapy-relevant alterations were identified in 1,130 of 1,250 (90%) of cases. Low or absent (0 or 1+ by IHC) MGMT, a biomarker of sensitivity to alkylating agents, was found in 130/219 pancreatic cases (59%), and in 450/991 (45%) of non-pancreatic NET. Low or absent (0 or 1+ by IHC) expression of RRM1, a biomarker of gemcitabine sensitivity, was found in 813/1,100 of NET (74%) and low or absent thymidine synthase, TS, a biomarker of fluoropyrimidine sensitivity, was shown for 793/1,096 (72%) of NET by IHC. Sequencing of tumors showed oncogenic mutations in BRAF (4/369 (V600E in 3 and G596R in 1), CTNNB1 (2/150), KIT (3/281), EGFR (1/178), FGFR2 (1/150), GNAS (1/150), HRAS (2/150), PIK3CA (6/343), RB (2/150) VHL (1/150), KRAS (10/125), NRAS (2/274), and APC (2/150) and amplifications of EGFR (46/686) and MET (4/236). Ki67 status and correlation between the site of origin and biomarkers will be presented. Therapies guided by mechanism-based biomarkers produced durable responses in documented cases: partial response (PR) &gt;1 year to imatinib in a patient with KIT-mutant metastatic NET, and in cases of MGMT low /TS low treated with streptozocine or temizolomide plus fluoropyrimidine chemotherapy, thus supporting the clinical relevance of target profiling in NET. Conclusions: Comprehensive multiplatform profiling of a large series (n=1,250) of NET, despite low frequency of individual biomarkers, identified clinically relevant targets in the majority of patients. Our results provide the basis for future clinical trials to assess the efficacy of biomarker-based therapy for NET.