tbuckley/cabot-search huggingface dataset:
A phase II study of docetaxel and carboplatin in patients with advanced non-small cell lung cancer after treatment with non-platinum regimens
Authors: T. Ikeda, M. Fukuda, M. Fukuda, Y. Soejima, S. Doi, S. Nagashima, Y. Nakamura, H. Soda, M. Oka, S. Kohno
Journal: Journal of Clinical Oncology (2009)

e19087 Background: Docetaxel and platinum is active in patients with non-small cell lung cancer (NSCLC) as first-line chemotherapy, and docetaxel is also effective in previously-treated patients. This study was designed to evaluate activity and toxicity of docetaxel and carboplatin as second-line chemotherapy in advanced NSCLC patients treated with non-platinum regimens. Methods: Patients with stage IIIB or IV NSCLC treated with non-platinum regimens, a performance status ≤ 2, and an adequate organ function were eligible. Patients were treated with docetaxel 50 mg/m 2 /day and carboplatin AUC 5 mg/ml/min on day 1 of each 21-day cycle. Primary endpoint was response rate. Results: Twenty-nine patients with a median age of 63 years were included. Median number of cycles for docetaxel and carboplatin was 3.2. Grade 3/4 neutropenia and anemia occurred in 21 (72.4%) and 2 patients (7.0%), respectively. Febrile neutropenia occurred in 2 patients (7.0%). Grade 3 non-hematological toxicity included diarrhea and peripheral neuropathy in each 1 patients (3.5%). Complete and partial response was observed in 1 and 4 patients, respectively. Overall response rate was 17.2% (95%CI: 5.9–35.8). Median survival time was 12.7 months (95%CI: 7.8–17.6) and 1- year survival rate was 52.5% (95%CI: 31.8–73.2). Conclusions: The combination of docetaxel and carboplatin as second-line chemotherapy may be promising in advanced NSCLC patients treated with non-platinum regimens. No significant financial relationships to disclose.
Empiric antimicrobial therapy for ventilator-associated pneumonia after brain injury
Authors: Antoine Roquilly, Fanny Feuillet, Philippe Seguin, Sigismond Lasocki, Raphaël Cinotti, Yoann Launey, Lise Thioliere, Ronan Le Floch, Pierre Joachim Mahe, Nicolas Nesseler, Tanguy Cazaubiel, Thierry Le Tourneau, Didier Lepelletier, Véronique Sébille, Yannick Mallédant, Karim Asehnoune
Journal: European Respiratory Journal (2016)

Issues regarding recommendations on empiric antimicrobial therapy for ventilator-associated pneumonia (VAP) have emerged in specific populations. To develop and validate a score to guide empiric therapy in brain-injured patients with VAP, we prospectively followed a cohort of 379 brain-injured patients in five intensive care units. The score was externally validated in an independent cohort of 252 brain-injured patients and its extrapolation was tested in 221 burn patients. The multivariate analysis for predicting resistance (incidence 16.4%) showed two independent factors: preceding antimicrobial therapy ≥48 h (p&lt;0.001) and VAP onset ≥10 days (p&lt;0.001); the area under the receiver operating characteristic curve (AUC) was 0.822 (95% CI 0.770–0.883) in the learning cohort and 0.805 (95% CI 0.732–0.877) in the validation cohort. The score built from the factors selected in multivariate analysis predicted resistance with a sensitivity of 83%, a specificity of 71%, a positive predictive value of 37% and a negative predictive value of 96% in the validation cohort. The AUC of the multivariate analysis was poor in burn patients (0.671, 95% CI 0.596–0.751). Limited-spectrum empirical antimicrobial therapy has low risk of failure in brain-injured patients presenting with VAP before day 10 and when prior antimicrobial therapy lasts &lt;48 h.
Intraperitoneal cisplatin and etoposide in the treatment of refractory/recurrent ovarian carcinoma.
Authors: B Reichman, M Markman, T Hakes, W Hoskins, S Rubin, W Jones, L Almadrones, M Ochoa, D Chapman, P Saigo
Journal: Journal of Clinical Oncology (1989)

To determine the efficacy of a 6-month course of combination intraperitoneal (IP) chemotherapy with cisplatin and etoposide in patients with refractory or recurrent advanced ovarian carcinoma, 67 patients were entered into this prospective, nonrandomized, single-institution trial. Cisplatin at 100 mg/m2 and etoposide at 200 mg/m2 were administered IP on day 1 every month for 6 months. Exploratory laparotomy was performed before protocol entry and was planned after the completion of 6 months of IP therapy to surgically document response. All patients had received prior intravenous (IV) chemotherapy with a cisplatin-based regimen. At protocol entry, 18 (27%) patients had surgically defined residual tumor (maximal tumor diameter) greater than 2.0 cm, 17 (25%) patients greater than 0.5 cm - less than or equal to 2.0 cm, and 32 (48%) patients less than or equal to 0.5 cm. Sixteen patients (24%) who had experienced a treatment-free interval of more than 1 year prior to study entry were considered as having recurrent disease and the remaining 51 (76%) patients were considered as having refractory disease. Toxicity was tolerable: four patients (6%) had nadir fever, three (4%) had culture-documented bacterial peritonitis, five (7%) had IP catheter-related complications, and 27 (40%) had an increase in serum creatinine greater than 1.5 mg/dL. Among the 57 patients who are fully evaluable for response, the overall surgically defined response rate, complete (CR), and partial response (PR), was 40% (23/57), and the CR rate was 21% (12/57). Among the patients with recurrent disease, eight of 13 (62%) responded, with responses seen among all categories of residual disease. Among the patients with refractory disease, 15 of 44 (34%) had surgically documented responses. However, responses were more frequent in patients with residual disease less than 0.5 cm; 11 of 20 (55%) versus four of 24 (17%) with residual greater than 0.5 cm, P = .019 (chi 2, one degree of freedom, Yates correction). The duration of the CRs ranges from 4 to 18+ months. Longer follow-up is needed to determine if there is any impact on survival.
Abstract 14908: The Success Rate of Automatic Pacing Threshold Determination Functions Differ among the Brands: What Was the Best Brand in a Far-East Single Center?
Authors: Naotaka Hashiguchi, Marehiko Ueda, Kazuo Miyazawa, Masayuki Ishimura, Takatsugu Kajiyama, Tomonori Kanaeda, Yoshio Kobayashi
Journal: Circulation (2014)

Introduction: Reliable automatic pacing threshold determination functions offer a reduced follow-up examination time and safe remote monitoring. Further, the success rate and accuracy of the automatic pacing threshold determination function have not been sufficiently clarified. Methods: We evaluated 456 patients (male/female: 269/187, age: 70.4±13.3 years, pacemakers/defibrillators: 341/115) with cardiac implantable devices that had an automatic pacing threshold measurement function (the atrium and ventricle/ ventricle only: 298/158). We measured their pacing thresholds with both the automatic and manual methods at periodic device examination visits. Patients who had a high threshold (&gt;4.0V/0.4ms) or out-of-range lead impedance (&gt;2000 or &lt;200Ω) were excluded from the analysis. Results: An automatic pacing threshold was obtained successfully in 206/274 (75.2%) patients in the atrium and in 392/443 (88.5%) in the ventricle. The automatic pacing threshold differed from the manual threshold by more than 1.0mV at the same pulse width in 12 (4.0%) patients in the atrium and in 5 (1.1%) in the ventricle. The success rate of the automatic pacing threshold determination differed depending on which generator manufacturer was used. The success rate for each manufacturer (Medtronic, St. Jude Medical, Biotronik and Sorin) was 167/173 (96.5%), 9/64 (14.1%), 30/37 (81.1%), and 0/0 in the atrium, and 223/224 (99.6%), 79/102 (77.5%), 68/85 (80.0%), and 22/32 (68.8%) in the ventricle, respectively. Regarding the success rate, Medtronic devices were superior to the others in both the atrium and ventricle (P&lt;0.001-P=0.039). St. Jude Medical devices were inferior to the others in the atrium (p&lt;0.001). There were no other significant factors affecting the success rate. The correlation between the pacing threshold measured by the automatic method and that by the manual method was significant in the atrium (r=0.558, P&lt;0.001) and ventricle (r=0.779, P&lt;0.001). Conclusions: The success rate of the automatic pacing threshold determination depended on which generator manufacturer was used. The measurable threshold values using the automatic method were acceptably correlated with those measured by the manual method.
Investigation on the advantage of interdisciplinary boards for patients receiving palliative treatment in a medical oncology department
Authors: K. Chouahnia, M. Luu, I. Wadoux, B. Clus, C. Fontaine, G. Des-Guetz, N. Baba-Hamed, R. Etessami, J. Morere
Journal: Journal of Clinical Oncology (2008)

20746 Background: Some of the patients receiving palliative treatment need social care as well as an adapted medical care. These cases are weekly debated in an interdisciplinary board with participants involved in different specialities (physicians, nurses, psychologists, social workers and dieticians). In this work, we display the results of a survey which evaluates the relevance of interdisciplinary boards aimed to a better taking into care of our patients. Methods: An investigation conducted during 16 months since the initiation of interdisciplinary boards in the medical oncology of the Avicenne Hospital. An anonymous questionnaire including 15 items was submitted for every subject to the staff in charge of the patient’s care. Results: 19/34 of interdisciplinary participants filled in the questionnaire. Among them, 14 attended at least once the interdisciplinary boards (73%). 5 specialists didn’t attend the boards owing to: lack of availability (40%), the day of the board not suitable (40%) and lack of convocation to attend the board (20%). Medical cases represented 65%, social cases 35% discussed during the boards. Among the participants, physicians (26%), nurses (58%), social workers, psychologists and dieticians (16%). In 64% of cases, the interdisciplinary boards were considered as beneficial tools to improve the taking into care of patients. Furthermore 86% of cases, holding such meetings at regular intervals was viewed as facilitating the circulation of information between different participants. In 93% of cases, participants come to believe that it is easy to take the floor during such interdisciplinary boards.The agenda as well as the duration of the meetings seem to be suitable for 85% of the participants. The week-day and frequency of the meetings were convenient for the 78% of cases. The decisions made during the interdisciplinary boards were communicated to the medical team in 86% of the cases, essentially verbally. Conclusions: The present survey demonstrates the benefit of interdisciplinary boards in a medical oncology in order to improve the taking into care of patients needing palliative as well as socially adapted care.Physicians and nurses are the most available health representatives for such meetings. No significant financial relationships to disclose.
mTOR inhibition affects primary liver cancer
Authors: M. Rizell, C. Cahlin, M. Olausson, L. Hafstrom, M. Andersson, P. Lindner
Journal: Journal of Clinical Oncology (2006)

14106 Background: Due to extent of tumour and underlying liver disease primary liver cancer, hepatocellular(HCC) as well as cholangiocellular(CCC), has extremely poor prognosis. The tyrosinekinase and mTOR inhibitor sirolimus, is registered for preventing allograft rejection. It retard experimental liver tumours in rats, and has antiangiogenic effects as well. Methods: Patients with a nonoperable HCC or CCC, with a Karnofsky &gt;70, and the diagnosis confirmed by biopsy or alfa-fetoprotein (&gt;700ug/ml) were eligible. Ethic committee approved the study and informed consent was signed. The daily Sirolimus dose was adjusted to a 6–10 μg/L through-concentration.Twenty patients were to be enrolled in a nonrandomized study. The primary endpoint was to detect a radiological tumor response rate, defined by RECIST criteria, and secondary endpoint was to study the safety profile. CT or MRI were repeated every third month. The study was approved by the Etic Committee of Göteborg University. Results: Eleven patients with HCC and nine with CCC were included. Overall respone rate was 5%, which ocurred in a patient patient with HCC. The PR lasted for 15 months (RR 9% for HCC). Four patients with HCC had SD for median 7 months (range 5–18). Of the patients with CCC four had SD. Median duration of SD was 4 months (range 1 - 7). Median survival for patients with HCC was 7 months (range 2–20) and CCC 4 months (range 2–24) Discussion: There is low evidence supporting the use of chemotherapy for primary liver cancer. For HCC, one PR and 4 SD in this pilot study indicate that sirolimus might be of interest to study in a phase II trial, since the toxicity of sirolimus was low. In the european SILVER study,the impact of sirolimus for patients transplanted for HCC will be clarified. Experimentally, the antiangiogenetic effects of sirolimus has been boosted by combining with 5-FU and gemcitabine. This might translate to impoved response rate also for liver cancer. Conclusions: This pilot study suggests that sirolimus have a tumour effect in patients with HCC. No significant financial relationships to disclose.
Phase II trial of paclitaxel in patients with adenocarcinoma of endometrium
Authors: E. Miyagi, R. Onose, K. Ochiai, S. Nozawa, K. Noda
Journal: Journal of Clinical Oncology (2004)

5121 Background: The antitumor activity and safety of paclitaxel monotherapy in patients (pts) with endometrial cancer still remain to be clarified. Methods: Eligibility criteria included: advanced or recurrent histopathologically proven endometrial adenocarcinoma with measurable lesion(s), age between 20 and 75, ECOG PS 2 or less, adequate organ functions, and written informed consent. No more than one regimen of prior chemotherapy was allowed. Pts received paclitaxel 210 mg/m2 by 3-hour infusion every 21 days. Results: Twenty-three pts were enrolled in the study. Pts characteristics include: endometrioid adenocarcinoma (15), adenoacanthoma (2), serous adenocarcinoma (2), clear cell adenocarcinoma (2), adenosquamous carcinoma (1) and mixed adenocarcinoma (1), Stage III/Stage IV/Recurrent = 2/4/17, PS 0/1/2 = 14/7/2. Thirteen pts had received prior chemotherapy. A total of 96 cycles of paclitaxel were administered, with a median of 4 cycles (range, 1–8). There were 7 PRs (30.4%, 95%CI: 13 - 53%), 10 NCs, 5 PDs and 1 NE. Median duration of response was 130 days (100–245 days) in 7 PR pts. Adverse reactions (grade 3, 4) included febrile neutropenia and constipation (8.7%, 2/23). Laboratory test abnormalities (grade 3,4) included neutropenia (78.3%, 18/23), leucopenia (47.8%, 11/23), anemia (13.0%, 3/23), decreased potassium (8.7%, 2/23), and decreased sodium (4.3%, 1/23). All adverse reactions were successfully managed by prolonging treatment interval, dose reduction, interrupting administration, discontinuation, and/or administration of G-CSF. Four pts discontinued treatment due to toxicity. Conclusions: The results suggest that three-hour intravenous infusion of paclitaxel 210 mg/m2 is well-tolerated and active therapy for advanced or recurrent endometrial cancer, and is worthy of further study in combination with carboplatin. No significant financial relationships to disclose.
Measurement of mutation-specific survival as a real-time cancer care quality indicator.
Authors: Jeremy Warner, Lucy L. Wang, Joseph Burden, Pam Carney, Scott Sobecki, Mia Alyce Levy
Journal: Journal of Clinical Oncology (2013)

30 Background: As targeted therapies become widespread in the treatment of cancer, tracking clinical effectiveness as a function of mutation status, outside of the research setting, is needed. We evaluated whether mutation-specific survival statistics could be derived in a completely automated fashion from electronic medical record data sources, for quality assurance and purposes preparatory to research. Methods: Patients with cancer mutation analysis obtained for clinical care at Vanderbilt University up to June 2013 were included. Informatics algorithms were developed to automatically extract tumor mutation status, cancer type, date of diagnosis, and date of death or date of last contact using multiple structured and unstructured clinical data sources including billing codes, narrative pathology reports, and the Social Security Death Index. Survival was modeled using Cox proportional hazards, stratified by mutation type; mutations occurring less than 10 times were aggregated into an “Other” category. Results: 2,636 out of 3,115,904 patients had sufficient data for inclusion. Date of death was recorded for 32% of patients; overall median follow-up was 19 months. The median mutation-specific survival for lung cancer and melanoma patients is shown in the Table. For lung cancer patients, EGFR mutation was associated with superior survival (HR 0.7, 95% CI 0.5-1, p = 0.05). For melanoma patients, GNAQ mutation was associated with inferior survival (HR 2.2, 95% CI 1.3-3.8, p = 0.006) whereas BRAF mutation was not statistically significant (p = 0.32). Conclusions: It is feasible to create survival curves based on cancer mutation status in a fully automated fashion for quality assurance and purposes preparatory to research. Further iterative improvements in the data extraction algorithms are continuing; updates will be presented. Future work will enable stratification by mutation subtype, treatment exposure, staging, and demographics. [Table: see text]
Local installation of small doses of streptokinase for treatment of thrombotic occlusions of long-term access catheters.
Authors: R N Rubin
Journal: Journal of Clinical Oncology (1983)

Small doses of streptokinase were infused locally into occluded long-term venous access catheters in seven patients with neoplasia who required such access for the administration of chemotherapy and blood products. This technique resulted in prompt resolution of clot in all patients, was easy to perform, and caused no hemorrhagic side effects or coagulation changes.
Trastuzumab mediated cardiotoxicity in the setting of adjuvant chemotherapy for breast cancer: A real world population-based study
Authors: D. Wadhwa, N. Fallah-Rad, D. Grenier, M. Krahn, T. Fang, R. Ahmadie, D. Lister, R. C. Arora, I. Barac, A. Morris, D. S. Jassal
Journal: Journal of Clinical Oncology (2008)

11522 Background: The use of trastuzumab in the adjuvant setting of HER-2 positive breast cancer has been demonstrated to reduce risk of recurrence by 50% and decrease overall mortality by 33%. Although these benefits are significant, the considerable risk of cardiotoxicity when trastuzumab is used following sequential anthracycline-based chemotherapy is often not well appreciated. Methods: The aim of the study was to retrospectively evaluate the incidence of cardiac dysfunction, characterize its natural history, and identify the degree of reversibility using cardiac MRI (CMR), in a real world population of HER-2 positive breast cancer patients receiving trastuzumab in the adjuvant setting. Results: Between 2005 and 2006, 152 patients (mean age 52±10 years) were identified to have received trastuzumab in the adjuvant setting. Approximately 24% (n=36) developed trastuzumab mediated cardiomyopathy, the majority of whom were asymptomatic. Factors that predicted the development of trastuzumab mediated cardiac dysfunction were a preexisting history of hypertension, smoking, and a family history of coronary artery disease. Within 3 months of treatment with trastuzumab, a difference in LVEF between the normal cohort and those patients who developed LV systolic dysfunction was observed (61±5 % vs. 51±8%, p<0.01). Among the 36 patients who developed trastuzumab mediated cardiomyopathy, 20 experienced full recovery of LVEF, 10 showed no change in LVEF and 6 had a progressive decline in LVEF at 6 month follow-up. The majority of patients had CMR findings of subepicardial linear delayed enhancement of the lateral wall of the left ventricle, confirming trastuzumab-mediated cardiac dysfunction. The delayed enhancement findings persisted for up to 6 months of follow-up, suggesting permanent injury to the myocardium. Conclusions: Approximately 1 in 4 women developed LV systolic dysfunction after treatment with adjuvant trastuzumab in this real world population-based study. The risks and benefits of treatment in each individual patient must be carefully considered, particularly in those with a history of smoking and hypertension, requiring vigilant monitoring of cardiac function while receiving trastuzumab. No significant financial relationships to disclose.
Surfactant release into the alveolar space protects the lung from ventilation-induced injury
Authors: Virginia Egido, Yeni Rojas, Almudena López-Sánchez, Antonio Ferruelo, Jose Ángel Lorente, Andrés Esteban, Cristina Casals
Journal: European Respiratory Journal (2012)

OBJECTIVE: The aim of this study was to investigate mechanisms involved in resistance to ventilation-induced lung injury.  METHODS: Sprague-Dawley rats were randomly exposed to a non-injurious low-stretch ventilation (V T  =9 ml/kg, PEEP=5 cm H 2 O) (n=12) and an injurious high-stretch ventilation (V T  =25 ml/kg, PEEP=0 cm H 2 O) (n=29). Animals were continuously monitored for a maximum period of 2.5 h. The high-stretch ventilation group (HV) was subdivided in two groups: 1) animals showing a substantial PO 2  reduction and peak airway pressure (Paw) increase, sacrificed at 60 min (HV60) (n=11); and 2) animals with insignificant PO 2  and Paw changes at 60 min (n=18), sacrificed at 150 min (HV150). Lung tissue, plasma, and bronchoalveolar fluid (BAL) were analyzed in the three groups. BAL provided native cytometric, inflammatory marker, and surfactant data.  RESULTS: The HV60 group was characterized by leakage of plasma proteins into the alveoli, presence of hyaline membranes, high increase of inflammatory markers in BAL (TNF-α, MIP-2, MCP-1, C-reactive protein, and acidic sphingomyelinase), pronounced decrease of alveolar macrophages, and an accelerated conversion of freshly secreted active surfactant to inactive surfactant. In contrast, the HV150 group was characterized by high amount of active surfactant, absence of edema, and normal PO 2 . These animals exhibited a slight decrease of alveolar macrophages and increase of some BAL inflammatory markers (IL6, TNF-α, MIP-2, and MCP-1).  CONCLUSIONS: These results suggest that increased surfactant release into the alveolar space safeguards the lung from ventilation-induced injury and that surfactant alteration might directly contribute to lung dysfunction.