tbuckley/cabot-search huggingface dataset:
Platinum and etoposide as second-line chemotherapy in advanced adult soft tissue sarcomas
Authors: M. Pavarana, A. Fraccon, T. Sava, P. Manno, R. Nortilli, R. Sabbioni, F. Valcamonico, M. Frisinghelli, M. Zaninelli, G. Cetto
Journal: Journal of Clinical Oncology (2004)

9063 Background: Advanced soft tissue sarcomas (STS) relapsing after first line chemotherapy are incurable. There is no standard treatment for patients (pts) relapsing after Doxorubicin and Ifosfamide first line chemotherapy, which are the most active drugs. Methods: 17 adults STS pts, relapsing after first line chemotherapy including Doxorubicin and Ifosfamide (mainly VAIA regimen) were treated with Platinum and Etoposide at our institution and retrospectively analysed. Median age was 40 (20–67) years. Histology were: leiomiosarcoma (3 pts), Ewing/PNET (7 pts), rabdomiosarcoma (4 pts), sinovialsarcoma (2 pts) and schwannoma (1 pt). Five pts had extremity lesions while 12 had trunk disease. At diagnosis 15 pts had advanced disease, one had microscopic residual and one was NED after surgery. Results: After first line chemotherapy, 2 pts achieved a complete remission, 4 a partial response, 2 were stable, 7 progressed and 2 were not evaluable; median time to relapse was 2 (0–21) months. Six and 10 pts had local and distant relapse, respectively. A median of 3 cycles (1–8) of Platinum and Etoposide were given. Toxicities were: 12% neutropenia G3, 12% trombocytopenia G4, 6% renal toxicity G2; one patient suffered from subarachnoid hemorrhage. We obtained 2 partial response (both rabdomiosarcoma, with overall survival of 3 and 15 months respectively), 3 stable disease, 9 progression disease and 3 not evaluable. Median time to progression was 2 (0–15) months. Conclusions: in STS pts relapsing after doxorubicin-ifosfamide regimen, Platinum and Etoposide as second line chemotherapy was a safe treatment permitting some responses (11%); Rabdomiosarcoma seemed to be the most responsive histology. No significant financial relationships to disclose.
Wide Complex Ventricular Rhythm in a Patient After Collapse
Authors: Anoop Muniyappa, Nora Goldschlager
Journal: JAMA Internal Medicine (2017)

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A phase 1 study optimizing the dosing of olaparib tablet formulation combined with cediranib in recurrent ovarian cancer.
Authors: Joyce Liu, Jung-min Lee, Weixiu Luo, Michael J. Birrer, Christin Whalen, Nicole D. Houston, Elizabeth Obermayer, Tatum Spagnoletti, William Thomas Barry, Elise C. Kohn, S. Percy Ivy, Ursula Matulonis
Journal: Journal of Clinical Oncology (2015)

5559 Background: PARP inhibitors and anti-angiogenics are clinically active in recurrent ovarian cancer (OvCa). Pre-clinical studies suggest these agents can synergize; a phase 2 study demonstrated that combination cediranib/capsule olaparib (C/O) increased progression-free survival (PFS) and response rate (RR) compared to olaparib alone. Olaparib clinical development will proceed using the tablet formulation; we therefore investigated the toxicities and recommended phase 2 dosing (RP2D) of C/O with olaparib tablets. Methods: Cediranib (C) once daily and olaparib (O) twice daily were administered orally in cohorts of 3 patients in a standard 3+3 Phase 1 design. Eligibility included pts with recurrent ovarian cancer. Pts had measurable disease by RECIST 1.1 or met GCIG CA125 criteria. No prior anti-angiogenics in the recurrent setting or prior PARP inhibitor were allowed. Results: 24 pts have been treated since May 2014 at 6 dose levels (C 20mg QD/O 200mg BID (3 pts); C 20mg QD/O 250mg BID (3); C 20mg QD/O 300mg BID (6); C 30mg QD/O 150mg BID (3); C 30mg QD/O 200mg BID (6); C 30mg QD/O 250mg BID). One DLT (gr 3 rotator cuff injury) occurred at the 30/200 dose level and two DLTs (1 > 7d hold for proteinuria; 1 gr 4 HTN and gr 2 intracranial hemorrhage) at the 30/250 dose level. Other related gr 3/4 adverse events (AEs) included HTN (5), vomiting (1), fatigue (1), myalgia (1), and thromboembolic event (1). Most common AEs included nausea (79%), fatigue (75%), diarrhea (58%), vomiting (42%), and HTN (42%). The RP2D levels are C 30mg QD/O 200mg BID and C 20mg QD/O 300mg BID. Best response in 21 evaluable OvCa pts (13 plat-resistant; 8 plat-sensitive) include 2 CR, 4 PR, 14 SD, 1 PD, including 1 CR, 2 PR and 2 SD in 5 evaluable pts at the 30/200 and 1 CR and 4 SD in 5 pts at the 20/300 dosing levels. Conclusions: RP2D for combination C/O tablets is cediranib 30mg/olaparib 200mg BID or cediranib 20mg/olaparib 300mg BID. Observed toxicities are consistent with those seen with combination using olaparib capsules. Preliminary assessment of activity demonstrated a 29% unconfirmed response rate in OvCa pts using a regimen that is safe and tolerable. An expansion cohort will enroll at the cediranib 30mg/olaparib 200mg BID level. Clinical trial information: NCT01116648.
Self‐Assembled Carbon Dot Nanosphere: A Robust, Near‐Infrared Light‐Responsive, and Vein Injectable Photosensitizer
Authors: Qingyan Jia, Jiechao Ge, Weimin Liu, Liang Guo, Xiuli Zheng, Shiqing Chen, Mingxing Chen, Sha Liu, Liping Zhang, Mengqi Wang, Hongyan Zhang, Pengfei Wang
Journal: Advanced Healthcare Materials (2017)

Self‐assembly “activated” carbon dot photosensitizer: a robust, NIR‐light responsive, and vein injectable carbon dot nanosphere (CDNS) photosensitizer with 1 O 2 quantum yield of 0.45 under 671 nm laser irradiation has been developed through self‐assembly using individual CD as building units. This study develops the biomedical applications of CD, highlights the self‐assembly for designing well‐defined CD‐based photosensitizers, and promotes future explorations of this CDNS photosensitizer in nanomedical and clinical applications.
Driving quality improvement with public reporting: Use of imaging tests outside guidelines for early-stage breast cancer in Ontario.
Authors: Colleen Bedford, Angel Arnaout, Rebecca Anas, Christina Catley, Mark Clemons, Craig Earle, Deanna Langer, Vicki Lee, Nicole Mittmann, Jennifer Stiff, Andrea Eisen
Journal: Journal of Clinical Oncology (2017)

193 Background: Most patients diagnosed with breast cancer will have early stage (stage I or II) disease, with low chance of distant metastases. Thus most guidelines, including Choosing Wisely, recommend against imaging tests for distant metastases in asymptomatic early stage breast cancer. Despite this, most (86%) of these patients in Ontario received these tests from which they are not likely to benefit and may result in investigations that can be invasive and delay treatment. Publicly reported indicators, such as those in Ontario’s Cancer System Quality Index (CSQI), can bring research findings to action by identifying areas for improvement and facilitating ongoing assessment. In practice, this can be challenging due to limitations in administrative data. Moreover, relatively few quality improvement indicators focus on efficiency, the dimension of quality looking at best use of resources to achieve desired outcomes. We sought to examine trends in the use of imaging tests in early stage breast cancer and to drive quality improvement efforts via public reporting. Methods: Data from the Ontario Cancer Registry, the Discharge Abstract Database and the Ontario Health Insurance database was used to identify how many Ontario breast cancer patients diagnosed with early stage breast cancer received staging tests from 2012–2014. Imaging tests included were ultrasound, CT scan, MRI, x-ray and bone scan. The results were subsequently shared with the Regional Cancer Centres and publically released in the CSQI. Results: From 2012 to 2014, 75.1, 72.7 and 71.3% respectively of early stage breast cancer patients received at least one imaging test for staging. This is much higher than the 5-10% of patients expected to need tests due to symptoms or comorbidities. While the regional variation ranged from 47-80%, the rates were high across the province with no clear pattern. Conclusions: Public reporting may be having some effect on overtesting, but rates remain high. Following outreach by the Cancer Quality Council of Ontario and Cancer Care Ontario, targeted regional interventions are being developed and implemented, the impact of which will be assessed and reported in future releases of the CSQI.
Evaluation of expression of DNA repair molecules as a prognostic factor for long-term survivors with glioblastoma multiforme (GBM) treated on RTOG protocols with irradiation and nitrosoureas
Authors: C. Ford, W. Seiferheld, A. K. Choucair, J. Hansen, B. Dabbas, C. Schultz, A. Schulsinger, M. Mehta, W. Curran
Journal: Journal of Clinical Oncology (2004)

1509 Background: Adding BCNU to irradiation appears to modestly increase one and two year survival in GBM patients. BCNU attaches a chloroethyl adduct to the O6 position of guanine followed by formation of a DNA interstrand cross-link. These lesions may be repaired by alkyl-guanine transferase (AGT) and nucleotide excision repair (NER)/homologous recombinational repair (HRR) pathways, respectively. BCNU-initiated apoptosis signaling depends on intact DNA mismatch repair (MMR). Defects in MMR and intact NER/HRR and p53 expression may be linked to BCNU insensitivity. We hypothesized that these may also be prognostic factors in GBM. Methods: We compared the expression of AGT, ERCC1 (involved in the DNA nicking step of NER/HRR), the MMR proteins hMLH1 and hMSH2, and p53 between tumor samples, selected from the RTOG tissue bank, from 28 long term (>18 months) and 35 short term (< 6 months) GBM survivors receiving irradiation and nitrosoureas on RTOG protocols. Tumor cell nuclear expression was determined by immunohistochemistry using the Chromovision automated cell imaging system. Results: The two groups vary in age (p=0.003) and KPS (p=0.02) but not extent of resection (p=0.12). Conclusions: Within this patient population the levels of the DNA repair molecules examined do not predict for long term survivorship. No interaction between MMR and AGT was observed. Larger future studies should examine the expression of these and additional factors involved in the repair of nitrosourea induced DNA adducts. No significant financial relationships to disclose.
The epidemiology, clinical findings and prognosis of colorectal cancer in Iran
Authors: P. Samareh Pahlavan
Journal: Journal of Clinical Oncology (2004)

9630 Background: This study was performed to evaluate the clinical features and outcome of patients with Colorectal cancer (CRC) in Iran. Methods: All cases of CRC presented to a main countryside referral University hospital (SGH) for cancers in Teheran, Iran between June 20,2000 and January 3,2003 were retrospectively reviewed to determine age, gender, subsite distribution, early symptoms, ethnicity, type of the CRC and the chemotherapy management. Results: A total of 200 patients were included .114 patients (57.0%) were male and 86 were female (43.0%) .Age ranged from 13–90 years with a mean of 55.15+/− 14.5 years.16.5% of patients were below 40 years of age.The tumors were classified as : appendix (n=4), cecum ( n=7), Right Cancers (RC), from the cecum to hepatic flexure (n=1), hepatic flexure ( n=2), Transverse Colon (n=19), Splenic Flexure (n=3), Left Colon (LC) from the Splenic Flexure down to Sigmoid (n=6), Sigmoid ( n=16), Rectum ( n=117), Rectosigmoid & Rectal lesions (n=16), and Colorectal lesions without known locations (n=9). Non-Mucinous Adenocarcinoma was the most common (n=181, 90%), followed by Mucinous AC (n=15), SCC (n=1), Carcinoid (n=1), Melanoma (n=1), Signet ring carcinoma (n=1). The most common presenting symptom was Rectal bleeding ( n=68, 34.5%) . 37% of patients had anemia at the time of diagnosis. 130 of patients underwent chemotherapy and the combination of 5-FU and Leucovorin was predominanat. (n=104, 52%) Younger patients significantly had more Mucinous AC (p=.008) and took more 5-FU.(p=0.05) Conclusions: We have no reports from the Epidemiology of CRC in Iran since 1977. the data suggested a younger age distribution for CRC . we found no significant difference between age, gender and type of cancer with subsite distribution . Distal (left-sided) CRC was more prevalent. 30.5% of patients were diagnosed by screening studies which highly suggests the procedure. 1 out of 200 patients was ethnically Jews and because of high risk in these people with a population of 26,354 in a 61M in Iran, so more investigation is needed. Anemia was less common in our population. younger patients received medical attention and 5-FU medication earlier and more. No significant financial relationships to disclose.
Association of Plasma 7-Ketocholesterol With Cardiovascular Outcomes and Total Mortality in Patients With Coronary Artery Disease
Authors: Jiayi Song, Duan Wang, Hongen Chen, Xiuwei Huang, Yuan Zhong, Nan Jiang, Chaogang Chen, Min Xia
Journal: Circulation Research (2017)

Rationale: 7-Ketocholesterol (7-KC), a form of cholesterol oxidation product, plays an essential role in the atherogenesis in animal models. Objective: We sought to determine the association of circulating 7-KC with clinical cardiovascular outcomes and total mortality in patients with stable coronary artery disease. Methods and Results: We measured the plasma 7-KC levels by high-performance liquid chromatography in a prospective cohort study of 1016 patients (mean age, 63.2 years; male 61.1%) with stable coronary artery disease who were recruited from December 2008 to December 2011 and followed up for a median of 4.6 years. We adjudicated myocardial infarction, hospitalization of heart failure, cardiovascular death, all-cause death, and composite end points of myocardial infarction/heart failure/death by review of medical records and death certificates. We used multivariable Cox proportional hazards analysis to compare the incidence rate of cardiovascular events and all-cause death according to the quartile of the plasma 7-KC. During the median 4.6 years follow-up, totally 221 participants (21.8%) experienced a cardiovascular event or death. The adjusted risk of the composite end points was higher in the highest 7-KC quartile than in the lowest quartile (hazard ratio, 1.76; 95% confidence interval, 1.42–2.21; P &lt;0.001). After adjustment for demographic and clinical variables and other biomarkers, including high-sensitivity C-reactive protein and NT-proBNP (N-terminal pro-B-type natriuretic peptide), 1 SD increase in the 7-KC level remained associated with a 36% higher rate of composite outcomes (hazard ratio, 1.36; 95% confidence interval, 1.22–1.48; P =0.007). Plasma 7-KC clearly improved various model performance measures, including C statistics, integrated discrimination, and category-free net reclassification. Conclusions: High 7-KC levels are associated with increased risk of cardiovascular events, total death, and composite outcomes in patients with stable coronary artery disease.
Assessment of the functional diffusion map (fDM) as an imaging biomarker for early stratification of glioma clinical response
Authors: B. D. Ross, D. A. Hamstra, T. L. Chenevert, B. A. Moffat, T. D. Johnson, C. Tsein, C. R. Meyer, S. Mukherji, L. Junck, A. Rehemtulla, T. S. Lawrence
Journal: Journal of Clinical Oncology (2006)

1518 Background: Current assessment of glioma treatment response relies on changes in the product of the maximal perpendicular tumor diameters at 2 months following treatment. Due to the fact that patients with malignant glioma have high mortality rates and a short median survival (about 41 weeks), the ability to stratify these tumors into responsive and non-responsive categories prior to treatment completion would allow for individualization of treatment. Changes in glioma water diffusion values were quantified using diffusion MRI as a biomarker for therapeutic-induced changes in tumor cellularity. Methods: A total of 37 patients with Grade III/IV supratentorial malignant gliomas (restricted to anaplastic astrocytomas (Grade III) and glioblastomas/sarcomas (Grade IV)) into a clinical imaging study. Standard and diffusion MRI scans pre-treatment and at 3 weeks post-initiation of chemo- and/or radio-therapy were acquired. Images were co-registered to pretreatment scans, and changes in tumor water diffusion values were calculated and displayed as a functional diffusion map (fDM) for correlation with clinical response. Results: Analysis of the patient data revealed that the fDM volumes of total detected diffusion change (V T ) was able to statistically discriminate (P&lt;0.001) between the stable disease (SD) and progressive disease (PD) patient populations 3 weeks into therapy. Patients classified as PD by fDM analysis at 3 weeks were found to have a shorter OS in the PD group compared with SD patients (median survival, 8.0 versus 18.2 months; p&lt;0.01). The fDM measurements provided an early biomarker for response, TTP and OS in malignant glioma patients. Conclusions: This novel imaging biomarker (fDM) was found to be a viable and early predictor of WHO clinical outcome. This clinical study strongly supports the hypothesis that fDM analysis provides a sensitive measure of therapeutic-induced changes in tumor cellularity, which can thereby serve as a predictive clinical surrogate marker for treatment response. Further evaluation of this imaging biomarker is ongoing. [Table: see text]
Impact of tumour thickness on survival after radical radiation and surgery in malignant pleural mesothelioma
Authors: Marc de Perrot, Zhi Dong, Penelope Bradbury, Demetris Patsios, Shaf Keshavjee, Natasha B. Leighl, Andrew Hope, Ronald Feld, John Cho
Journal: European Respiratory Journal (2017)

Tumour thickness was assessed to determine if this parameter could refine patients' selection for multimodality therapy in malignant pleural mesothelioma. We reviewed 65 consecutive treatment-naïve malignant pleural mesothelioma patients undergoing surgery for mesothelioma after radiation therapy (SMART). Total tumour thickness was determined by measuring the maximal thickness on nine predefined sectors on the chest wall, mediastinum and diaphragm. After a median follow-up of 19 months, 40 patients (62%) developed recurrence and 36 died (55%). Total tumour thickness, ranging between 2.4 and 21 cm (median 6.9 cm), correlated with tumour volume (p&lt;0.0001, R 2 =0.29) and maximum standardised uptake value (p=0.006, R 2 =0.11). Total tumour thickness had a significant impact on overall survival and disease-free survival in univariate analysis. In multivariate analysis, total tumour thickness remained an independent predictor of survival (p=0.02, hazard ratio (HR) 1.12, 95% CI 1.02–1.23) and disease-free survival (p=0.01, HR 1.13, 95% CI 1.03–1.24) along with epithelial histologic subtype (p&lt;0.0001, HR 0.25, 95% CI 0.13–0.50) and pN2 disease (p=0.03, HR 2.15, 95% CI 1.07–4.33). Diaphragmatic tumour thickness correlated best with time to recurrence (p=0.002, R 2 =0.22) and time to death (p=0.003, R 2 =0.2). The impact of tumour thickness on survival and disease-free survival independent of histologic subtypes and nodal disease is extremely encouraging. This parameter could potentially be used to refine the clinical staging of malignant pleural mesothelioma and optimise patient selection for radical treatment.
Survival patterns by line of treatment of stage IIIb/v NSCLC patients from community U. S. oncology practice.
Authors: Shraddha Chaugule, Susan H Foltz Boklage, Charles Kreilick, Sean D Sullivan, Scott David Ramsey, Sally Haislip, James W. Gilmore, Stephen Szabo, Syam Sarma, Carl V Asche, Brian S. Seal
Journal: Journal of Clinical Oncology (2012)

e18097 Background: Lung cancer is the most common cause of cancer-related death in men and women worldwide. 80% of the lung cancer patients are diagnosed with NSCLC. Patients have varying survival results from multiple lines of treatment. The objective of this study was to evaluate in a real world context, treatment patterns with survival, and the impact of adding a third line of chemotherapy to a stage III/IV NSCLC population. Methods: The Georgia Cancer Specialist database (2005-2011) was used. Patients with stage III or IV primary NSCLC and treated with chemotherapy were followed from initial NSCLC diagnosis until death, study end or lost to follow-up. Patients were stratified into lines and type of protocol for treatments. Kaplan-Meier curves were used to compare the overall survival results between lines of therapy. Results: A total of 291 patients with advanced NSCLC were identified and included in the primary analysis. Of these, 40 patients received third line therapy. The most commonly used treatment regimens in third line were Pemetrexed with 11 patients (3.8%), Docetaxel with 10 patients (3.4%), Gemcitabine with 4 patients (1.4%), Vinorelbine with 3 patients (1%) Cisplatin/Gemcitabine/Bevacizumab with 2 patients (0.7%). No single treatment regimen was predominantly used in third line. No association of survival gain was seen in patients who received third line therapy over those who received second line therapy (Log-Rank test P=0.4926) Conclusions: In a large EMR physician practice based database of advanced NSCLC patients, we failed to find a difference in the median overall survival of patients who received third line therapy compared to those who received second line therapy. Limitations include a small sample size and no standardized timing of diagnosis and treatment. The lack of a standard of care in third line therapy necessitates the need of further randomized controlled clinical studies to establish a benefit for a particular combination.