tbuckley/cabot-search huggingface dataset:
Preventing Overdiagnosis and Overtreatment: Just the Next Step in the Evolution of Breast Cancer Care
Authors: Rita A Mukhtar, Jasmine M Wong, Laura J Esserman
Journal: Journal of the National Comprehensive Cancer Network (2015)

The problem of overdiagnosis and overtreatment has been highlighted in breast cancer and many other cancer types, most notably prostate cancer. Addressing this problem presents an opportunity to continue the evolution of breast cancer care. Advances in technology, such as molecular subtyping, have increased the understanding of breast cancer biology and the range of associated behavior, and have provided tools that allow greater personalization of treatment. This article identifies 3 areas of breast cancer care where opportunity currently exists to refine management strategies and help decrease overtreatment and overdiagnosis: the use of adjuvant-external beam radiation in invasive breast cancer, the application of aggressive treatment for all ductal carcinoma in situ, and the authors' approach to breast cancer screening. Personalizing treatment based on patient and tumor characteristics holds promise for minimizing harms and maximizing benefits. This approach will allow continual improvement and ultimately result in providing the right treatment for each patient.
Palliative radiotherapy in stage III/IV NSCLC: Dose, fractionation, and survival.
Authors: C. R. Lewanski, M. Singhera, S. Dubash, A. C. Thompson, F. Bowen, B. Mann, R. Mathur, M. Rudolf, S. O'Donnell, T. White
Journal: Journal of Clinical Oncology (2010)

e18064 Background: Radiotherapy (RT) is frequently used to palliate the symptoms of advanced stage 3 and 4 NSCLC. A number of fractionation regimens are employed in the United Kingdom, although the optimal dose and fractionation remains unclear. Methods: A single-center, single-consultant practice in the United Kingdom was reviewed retrospectively (2003-2009). A total of 343 patients received palliative RT for stage 3 or 4 NSCLC either alone or as part of bimodality therapy with chemotherapy/TKI's. All patients were CT planned and treated with opposed photon fields. Four dose/fractionation regimens were examined. The inter-relationship with systemic therapy was reviewed, with the majority of patients receiving RT as consolidation following systemic therapy. Results: See Table. Conclusions: Significantly improved survival was observed in the multifraction regimens as compared to single-fraction treatments. A trend to improved survival over other regimens was observed in the 36Gy/12 fraction group. Significantly higher systemic therapy usage was noted in the 10 and 12 fraction regimens, a result primarily of better patient performance scores. The strong correlation with systemic therapy usage in improving outcomes may play a significant role when employed sequentially with RT. Regimen No. patients Mean age (yrs) Median survival (months) % receiving chemotherapy % receiving TKI % total receiving systemic therapy 10Gy single fraction 45 75.6 (58- 92) 4.0 (0-18) 6.7% 0% 6.7% 20Gy in 5 fractions (1 week) 176 70.5 (37- 93) 8.0 (0-77) 22.2% 3.9% 26.1% 30Gy in 10 fractions (2 weeks) 93 77.5 (39-94) 9.0 (0-47) 52.1% 10.7% 62.8% 36Gy in 12 fractions (2.5 weeks) 29 61.2 (43-78) 13.0 (3-43) 62.1% 10.3% 72.4% No significant financial relationships to disclose.
Attitude of their members is the critical factor
Authors: H. Dudley
Journal: BMJ (1995)

EDITOR,--I agree with the subtitle of K G M M Alberti's editorial on local research ethics committees—it is “time to grab several bulls by the horns.”1 Before the profession and others can do so, however, we need to be much more precise about our thinking.

Firstly, in Editor's choice the BMJ's editor is guilty of a basic semantic error: those who are asked to look at issues of experiment on humans are not members of “ethical committees” in …
Multi-center prospective study on sentinel node navigation surgery in early breast cancer
Authors: S. Imoto, M. Kitajima, T. Aikou, Y. Kitagawa
Journal: Journal of Clinical Oncology (2007)

606 Background: Sentinel node navigation surgery (SNNS) is a standard technique to identify lymph node metastases in clinically node-negative breast cancer. However, the dye and radiopharmaceuticals for lymphatic mapping commonly used in Western countries are not available in Japan. Methods: To assess the optimal lymphatic mapping and the outcome after SNNS, the Japanese society for SNNS conducted a non-randomized multi-center prospective study on SNNS in early breast cancer. Primary endpoint is to evaluate the success rates and adverse events associated with various lymphatic mapping and SNNS, and secondary endpoint is to observe the outcome of patients who underwent SNNS during 5 years. After the protocol was approved by institutional review board, SNNS had been registered between July 2004 and October 2005. Results: Fourteen hundred and sixty-eight cases had pre-registration from 65 investigators at 23 institutions. As 46 cases were withdrawn for some reasons and 11 cases were diagnosed as benign disease, 1,411 cases were finally entered in this study. Dyes used for lymphatic mapping were indigocarmine, indocyanin green, patent blue, and isosulfun blue, and radiopharmaceuticals were 99m-technetium-labelled tin colloid, human serum albumin, and phytate. In 19 cases, superparamagnetic iron oxide was used for MRI- guided SNNS. As of December 2006, 98% of clinical report forms were analyzed. Dye-guided SNNS was performed in 240 cases, radio-guided SNNS in 56 cases, and combined method in 1,016 cases. Overall success rate was 99%. SNNS alone was treated in 1,138 cases (82%) and SNNS followed by axillary lymph node dissection in 258 cases (12%). Breast-conserving surgery was undergone in 1,175 cases (85%) and total mastectomy in 217 cases (15%). Dye-induced allergic adverse events were not reported. Postoperative adverse events of bleeding, wound infection and seroma were observed in about 1 % of cases, respectively. Conclusions: Dye-guided and/or radio-guided SNNS proved reliable for lymphatic mapping in breast cancer. The prognosis of all cases will be observed until 2010. No significant financial relationships to disclose.
Monitoring oxidative stress in the lung: Changes in superoxide dismutase (SOD) activity during the course of acute exacerbations in COPD
Authors: Imre Barta, Orsolya Drozdovszky, Balázs Antus
Journal: European Respiratory Journal (2013)

Background: SOD activity is a well established marker of oxidative stress in several pathological conditions. The enzyme catalyzes the transformation of superoxide anions into hidrogen peroxide and molecular oxygen and thus plays a key role in preventing oxidative damage to cells.  Rationale: We aimed to assess local SOD activity as a potential marker of oxidative stress in the lung of COPD patients in exacerbation. Additionaly, we were interested to see if changes in SOD activity could aid the monitoring of recovery of these patients.  Methods: COPD patients (N=24; age: 69±2.3; pack-year: 27±4.5; GOLD I-IV) suffering an episode of acute exacerbation were enrolled. Sputum samples were first taken before treatment was started and again at the time of discharge from the hospital. SOD activity was measured in sputum supernatant by means of an enzyme activity assay and results were compared to those found in stable COPD patients and healthy controls.  Results: SOD activity was significantly higher in COPD patients with exacerbation as compared to controls [0.069 (0.030-0.148) U/ml vs. 0.005 (0-0.073) U/ml and 0.010 (0-0.043) U/ml]. Upon treatment enzyme activity had not changed significantly. No correlations were found between SOD activity and lung function or other clinical parameters.  Conclusions: Sputum SOD activity is elevated in COPD patients in a state of exacerbation but apparently independent of disease severity and the extent of systemic inflammation. SOD could thus potentially be used as a marker of exacerbation, however it is not sensitive enough to aid monitoring the improvement of the condition during the time-frame of a typical hospital stay.
Gene expression analysis to identify the pharmacodynamic effects of docetaxel on the Rho signal pathway in human lung cancer patients
Authors: T. Shimoyama, N. Yamamoto, T. Hamano, T. Tamura, K. Nishio
Journal: Journal of Clinical Oncology (2005)

2002 Background: Docetaxel (DTX) binds to β-tubulin, resulting in mitotic arrest. DTX is known to act on signal transduction pathways and to have an additional mode of action. We monitored gene expression in peripheral blood cells from lung cancer patients treated with docetaxel to analyze the pharmacodynamic activity of DTX. Methods: To define the specific changes associated with DTX exposure, we used a customized cDNA microarray analysis to compare the gene expression profiles of 21 paired samples (before and after treatment) of peripheral blood mononuclear cells obtained from lung cancer patients. Results: Using a supervised, machine-learning classification algorithm, we built a multi-gene classifier that accurately distinguished (91%) treated samples from untreated samples and identified 11 significant marker genes (P = 0.002). All of the selected genes were associated with Rho or Rho-associated genes possibly involved in the regulation of microtubule dynamics, apoptosis, and cytoskeleton processes. A discriminating analysis revealed correlations between five of the 11 gene expression profiles and the degree (78–29% of the control value) of lymphocytopenia induced by DTX. Conclusions: DTX specifically modulated the expression levels of genes involved in the Rho signal pathway in peripheral mononuclear cells from lung cancer patients. The DTX-induced alterations in gene expression were correlated with the degree of lymphocytopenia. The pharmacodynamics proof-of-principle study of DTX was successfully demonstrated. The genes identified by this study may become important biomarkers of other taxanes in the field of pharmacogenomics and toxicogenomics. No significant financial relationships to disclose.
Pulmonary contusion – A risk factor of mortality in blunt thoracic trauma
Authors: Ivan Novakov, Silviya Novakova, Philip Shterev
Journal: European Respiratory Journal (2014)

Despite the development of intensive respiratory therapy, the mortality of patients with blunt thoracic trauma still remains in a very high level.   The aim  of this study is to present the role of pulmonary contusion as a risk factor of mortality in blunt thoracic trauma.   Material and Methods.   This 3-year retrospective study (September 2010 year – October 2013 year) was performed on the base of a group of 212 hospitalized patients with blunt thoracic trauma. Imagine diagnosis (chest x-ray, chest computed tomography) and autopsy (gross pathology and histological examination) were used to establish the pulmonary contusion and post-contusional lung pathological changes.   Results.   Pulmonary contusion was established in 139 of patients (65, 57 %). The death was established in 36 of patients with blunt thoracic trauma – 16, 98 % mortality rate. Death up to 72 nd  hour of blunt thoracic trauma was established in 9 of patients, 5 of whom with severe pulmonary contusion. Pulmonary contusion with posttraumatic lung edema (10 cases) and posttraumatic pneumonia (17 cases) were the cause of the death after 72 nd  hour of blunt thoracic trauma. Calculated odds ratio of 5, 15 presented pulmonary contusion as a risk factor of death in blunt thoracic trauma.   Conclusion.   This study confirmed a very high mortality rate of patients with blunt thoracic trauma. It convincingly presented the pulmonary contusion as a risk factor of death in patients with blunt thoracic trauma.
Gene expression profiling associated with risk of recurrence in patients with colorectal cancer
Authors: M. A. Gordon, W. Zhang, M. Karaman, J. Yun, O. Press, K. Rhodes, D. Vallböhmer, S. Iqbal, J. Hacia, H. J. Lenz
Journal: Journal of Clinical Oncology (2005)

3602 Background: Early identification of patients at increased risk for recurrence remains a central issue in the treatment of colorectal cancer. Altered expression levels in cancer-related genes have emerged as potential markers in determining risk of recurrence. However, due to the large and complex variety of pathways that influence colon cancer progression, a set of molecular markers has not been established as a basis for clinical prognosis. The use of microarray technology addresses this problem by taking a comprehensive approach to examining gene expression rather than a restricted pathway approach. We analyzed gene expression profiles of 38 colorectal cancer patients using microarrays to determine differential expression patterns of recurrence versus recurrence-free patients. Methods: 38 patients receiving adjuvant chemotherapy were selected, of which 14 experienced recurrence and 24 did not. RNA was extracted from fresh frozen tumor tissue and microarray analysis was conducted using Affymetrix U133A genechip containing 22,000 probe sets. Cluster analysis was performed to differentiate between recurrence and recurrence-free patients. In addition, significance analysis of microarrays (SAM analysis) was conducted to establish an expression profile based on recurrence. Genes with a greater than 1.5 fold difference in expression from the standard deviation were considered significant, with a false discovery rate of less than 10%. Results: By SAM analysis, 87 genes were found significantly differentially expressed in recurrence vs. non-recurrence patients. The 87 genes do not all associate functionally but rather are involved in a variety of cancer-related pathways, including angiogenesis, cell proliferation, apoptosis, cell cycle regulation, and cell adhesion. Additionally, clustering showed a mild correlation between recurrence and recurrence-free patients. Conclusions: These results demonstrate the ability of expression profiling using microarrays to predict recurrence in colorectal cancer. Expression profiling may be used in combination with traditional pathologic staging to more accurately characterize disease status and hence individualize treatment at the genetic level. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Chiron, Genentech, Response Genetics Lilly Oncology, Pfizer, Roche, Sanofi NCI, NIH
Adverse event (AE) assessment lists for clinical trials (CTs) influence AE reporting rates: An evaluation of AE data collected on North Central Cancer Treatment Group CTs
Authors: M. R. Mahoney, D. J. Sargent, M. E. Campbell, B. P. Hobbs, J. W. Kugler, S. R. Alberts, J. C. Buckner
Journal: Journal of Clinical Oncology (2007)

6517 Background: In NCCTG CTs a subset of AEs are assessed at each patient (pt) evaluation based on the known safety profile of agents(s). The NCCTG routinely pre-fills the “known” AE list onto CT Case Report Forms (CRFs). Newly identified AEs may expand the AE assessment list for ongoing CTs. Our survey of NCCTG AE data (JCO 2005), demonstrated that 85% of AEs reported were pre-filled on CRFs, of which, 83% did not actually occur (Grade 0). Extending this work, we evaluated the influence of pre-filling AEs on CRFs, relative to the final AE rates reported. Methods: Our non-random sample contains 507,899 AEs collected from 1/99–6/06 on 74 NCCTG CTs, 13 of which had AEs added to the CRF pre-fill list during the CT (2,604 pts, 3 Ph I/II, 8 Ph II, 2 Ph III, 9 investigational agents). Results: An average of 2.8 AEs (range 1–6) were added to CRFs for ongoing CTs, primarily for Oxaliplatin induced AEs. 58% (21/36) of AEs added during a CT were not reported prior to the addition, 22% (8) were not reported afterwards. 5 CTs had significantly higher AE rates (p&lt;0.01) after expanding the AE list, most notably for required blood chemistries (SGOT/alk phos/creatinine/bilirubin 14.2 vs 0.72%). Overall, the same AEs were 4-fold (range 0–25) as likely to be reported when pre-filled on the CRF. Regardless of pre-filling, only 6% of the newly required AEs were Gr 3+. Conclusions: Our data suggest a significant difference between the AE rates reported if included in the CT CRF assessment list. This may significantly influence the reported results of a CT, explaining differential AE rates reported across CTs of the same agent(s). A prospective study is planned to formally evaluate this observation. Supported by NIH Grant CA25224. No significant financial relationships to disclose.
Assessment and training of physicians in the “art of oncology”: Results from a psychosocial seminar in first-year of fellowship
Authors: A. B. Moadel, E. Greenwald
Journal: Journal of Clinical Oncology (2004)

6039 Background: In an effort to identify and address the psychosocial training needs of oncology fellows in an urban cancer center, a Psychosocial Needs Survey and Seminar were developed and implemented. Methods: Between 1998–2003, all oncology fellows (n=38) were assessed at the year's start about their self-reported frequency and comfort in discussing several psychosocial issues with patients. They then attended a monthly or biweekly, 10-session psychosocial seminar taught by an oncologist and health psychologist after which they were re-assessed (n=27). Results: The fellows indicated they discussed the following issues \(\underline{\mathrm{never\ or\ at\ initial\ visit\ only}}\) according to pre- and post-seminar assessment, respectively: psychological services (22% vs 0%, p<0.020); sexual functioning (69% vs 48%); patient's beliefs about cancer/treatment (28% vs 14%); spiritual/religious services (61% vs 45%); and alternative medicine (47% vs 43%). Based on pre- and post-seminar, fellows reported \(\underline{\mathrm{discomfort}}\) in discussing poor prognosis (33% vs 10%, p=0.044); lack of treatment options (50% vs 24%, p=0.052); end-of-life issues (39% vs 10%, p=0.017); initial diagnosis: (22% vs 5%); sexual functioning (43% vs 33%); emotional adjustment (14% vs 5%); alternative medicine (46% vs 25%); and spiritual issues (29% vs 35%). Most (82%–100%) fellows found the seminar topics “informative/very informative”, with the readings, videos, discussion, role-playing, relaxation exercises described as “helpful/very helpful” by 72%–96%. Conclusions: Based on self-reported patient care practices, first-year oncology fellows demonstrate room for growth in the “art of oncology”. Results suggest that psychosocial training exposure throughout the first year of fellowship may raise physicians' awareness and comfort in addressing psychological support and advanced disease issues. Further exploration regarding attitudes and barriers to addressing spiritual needs, sexual functioning, and alternative medicine is warranted. No significant financial relationships to disclose.
Stratification of 5-year cancer detection rate in an organized breast screening program based on Gail model risk factors.
Authors: Rasika Rajapakshe, Brent Parker, Cynthia Araujo, Stephanie Ruscheinsky, Steven McAvoy, Tanja Hoegg, Andy Coldman, Christine Wilson
Journal: Journal of Clinical Oncology (2012)

7 Background: The Gail model has been validated in the United States and several European countries, but to our knowledge, it has not been validated in organized breast screening programs in Canada. The Screening Mammography Program of British Columbia (SMPBC) records participant data from a questionnaire based on Gail model parameters (which include family and personal medical history). This study investigates whether the Gail model is a valid tool to predict the breast cancer risk for the population undergoing screening mammography in the province of BC. Methods: Client information of the 223,349 British Columbian women who participated in the year 2000, along with their tumor status from 2000-2004, was extracted from the provincial database. A software program was developed to rapidly calculate the absolute 5-year Gail score from questionnaire data. Participant data was separated into .5% risk intervals and also into quintiles based on increasing Gail scores, and the mean absolute risks were compared to the actual five year rate of cancer as detected by the SMPBC. Results: Overall, goodness of fit between Gail score and SMPBC detection (E/O) across the categories can be rejected (χ2=247.9, df=9, p value &lt; .001). The Gail model significantly underpredicts the cancer detection for risk categories up to 2%, however it provides a sufficient fit for categories 2%-4% as the E/O ratio is not significantly different from 1.0 in these intervals. For the highest risk interval, categorized as greater than 4% risk, the model significantly overpredicts cancer detection. Additionally, when presented in quintiles, the Gail model under-predicts risk in all but the highest quintile (1.77-11.43% risk range). Conclusions: Our results, based on participants of SMPBC, suggest that the Gail model significantly under-predicts cancer detection. Although this model provides a sufficient fit for women with a Gail score between 1.51-4%, it does not predict breast cancer risk accurately for low and high risk women in the Screening Mammography Program of BC.
Abstract 16942: Effects of BMPR2 Mutations on Global MicroRNA Expression Profiles in Blood Outgrowth Endothelial Cells from Patients with Pulmonary Arterial Hypertension
Authors: Kenny Schlosser, Mark L Ormiston, Nicholas W Morrell, Duncan J Stewart
Journal: Circulation (2012)

Background:  Mutations of the bone  morphogenetic protein receptor 2 gene ( BMPR2 ) are  found in patients with heritable (H) or idiopathic (I) pulmonary  arterial hypertension (PAH). However, their role in abnormalities of  endothelial cell (EC) growth and survival in PAH is unclear.  Therefore, blood-outgrowth endothelial cells (BOECs), which closely resemble mature endothelial cells, were used to study patient-specific effects of  BMPR2  mutations on endothelial microRNAs (miRNA), which are recognized to be key regulators of gene expression.   Hypothesis:  Disease-specific alterations in miRNA expression profiles in BOECs from patients with HPAH or IPAH, with and without  BMPR2  mutations, contribute to the previously reported abnormalities in EC growth and survival in this disease.   Methods:  BOECs were derived from the peripheral blood mononuclear cell fraction isolated from 7 patients (4 HPAH with  BMPR2  mutations, and 3 IPAH) and 5 healthy controls (including 1 unaffected  BMPR2  mutation carrier). Cells were characterized by cobblestone morphology and surface marker profile (cd31+/cd45-/cd14-/cd34+/KDR+). 1066 miRNAs were measured using an (RT)-qPCR array platform (Qiagen), and normalized with a mean-centering restricted method.   Results:  767 ± 30 miRNAs were detected in BOECs from the 12 participants (PCR Cq cutoff  BMPR2  mutations vs. controls (p BMPR2  mutation carrier.   Conclusion:  A global analysis of miRNAs in BOECs revealed distinct profiles in IPAH and HPAH patients, with both disease- and  BMPR2  mutation-specific patterns of expression. These data suggest that unique miRNAs may contribute to alterations in endothelial gene expression that underlie abnormalities in EC growth and survival, and may be novel targets for therapeutic and biomarker development.