tbuckley/cabot-search huggingface dataset:
First interim report on the randomized EORTC 62961/ESHO-RHT 95 Intergroup Study (phase III) combined with regional hyperthermia (RHT) versus chemotherapy alone in the treatment of high-risk soft tissue sarcomas (HR-STS) in adults
Authors: L. H. Lindner, M. Schlemmer, P. Hohenberger, P. Wust, S. Abdel-Rahman, M. Schmidt, I. Judson, J. Y. Blay, J. Verweij, R. D. Issels
Journal: Journal of Clinical Oncology (2004)

9015 Background: Based on our phase II results, RHT is considered a promising neoadjuvant treatment strategy for HR-STS and is being evaluated in a prospective RCT (phase III). We are now reporting the results of the first interim analysis after recruitment of 146 patients (pts) with HR-STS (tumors ≥ 5 cm, grade 2 or 3, extracompartmental, and deep). Methods: Between July/97 and Nov/01 all pts have been randomised to receive four pre- and post-operative cycles EIA (etoposide: 250 mg/m2; ifosfamide: 6 g/m2; adriamycin: 50 mg/m2) either combined with RHT (74) or EIA alone (72). Pts were stratified by extremity (E=64) vs non-extremity (Non-E=82), and by primary (S1=65) vs recurrent (S2=29) vs previously inadequate (R1/R2) resected (S3=52) tumors. Results: At Nov/03 224 pts of planned 340 pts (170 pts per arm) have been randomized. For 141 pts entering the protocol treatment, 95% (preoperative) and 89% (postoperative) of prescribed EIA cycles could begiven. 80% (preoperative) an 66% (postoperative) of the planned numbers of RHT applications were performed. Hematological toxicity (grade 3/4) was seen in 17 pts consisting primarily of leucopenia (13) and thrombopenia (4). In 102 pts evaluable (not evaluable S3=33 or other=11) for response after completion of 4 EIA with or without RHT, objective response rate was 28% (2 CR; 27 PR). In addition, 7 pts showed MR (7%), 57 pts SD (56%) and 9 pts PD (6%). Of 135 assessable pts, 33% received no surgery (32 pts S3/R1 and 13 pts other reasons), but 61% received conservative resection (83) and 5% were amputated (7) with 10% histopathological complete necrosis (9). At median follow-up of 36 months (cut-off 4/03) the 3–year local progression free rate (LPFR), distant progression free rate (DPFR), and overall survival (OS) for E are 86.6% (95% CI: 77.3–96.0%), 78.1% (95% CI:67.0–89.1%) and 77.3%(95%CI:65.8–88.7%) andfor Non-E are 40.9%(95% CI:28.1–53.7%), 54.9%(95% CI:40.3–69.5%) and 41.5% (95% CI:28.9–54.0) repectively. Conclusions: The neoadjuvant EIA regimen with or without RHT is feasible and tolerable in the majority of pts. While this is a preliminary report, the estimated 3-year LPFR, DPFR and OS in local-advanced HR-STS pts are encouraging. The second interim analysis is planned for 247 pts. No significant financial relationships to disclose.
The impact of cetuximab on the capecitabine plus oxaliplatin (XELOX) combination in first-line treatment of metastatic colorectal cancer (MCC): A randomized phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)
Authors: M. Borner, W. Mingrone, D. Koeberle, R. Von Moos, D. Rauch, P. Saletti, R. Herrmann, D. Dietrich, D. Lanz, A. Roth
Journal: Journal of Clinical Oncology (2006)

3551 Background: XELOX is a valuable alternative to continuous infusion FOLFOX type regimens in the treatment of MCC (Borner et al, JCO 2002, 1759). Cetuximab is an EGFR antibody, which has been shown to improve the efficacy of chemotherapy. A phase II study in first-line treatment of MCC has demonstrated a high response rate combining cetuximab with FOLFOX (Tabernero et al, Proc ASCO 2004, 3512). Methods: Multicenter, randomized two-arm phase II trial: OXA 130 mg/m 2 day 1 and oral CAP 1000 mg/m 2 bid days 1–14 every 21 days alone or in combination with cetuximab 250 mg/m 2 weekly after a loading dose of 400 mg/m 2 . Treatment was limited to a maximum of 6 cycles. With 37 patients in each arm, the power was 90% to select the truly better arm if the true between-arm difference in response rate (RECIST) is at least 15%. The study was open for accrual until October 2005. Results: We present here the results of 74 patients included in the study. In 67 patients the first response data are available (investigators’ assessment after 3 cycles). The two arms are well balanced for relevant patient, disease and treatment characteristics. The study treatment was well tolerated with grade 3/4 toxicities in &lt; 10% of the cycles in each arm. The frequency of side effects was balanced, but with more frequent skin toxicity in the cetuximab arm (6% versus 0% grade 3/4). Conclusions: Cetuximab seems to positively interact with XELOX in terms of efficacy but not toxicity. The cetuximab/XELOX combination appears to be a valuable option in first-line treatment of MCC especially if high response rates are a primary objective. This trial was supported in part by Merck KGaA and Sanofi-Aventis Switzerland. [Table: see text] No significant financial relationships to disclose.
Meningitis after Splenectomy
Authors: C D Selby, P J Toghill
Journal: Journal of the Royal Society of Medicine (1989)

Five splenectomized patients suffered six episodes of bacterial meningitis with positive cerebrospinal fluid cultures. They were admitted to the Nottingham hospitals between 1974 and 1985. The infecting organism in all cases was Streptococcus pneumoniae. Only one patient, who survived, had had pneumococcal vaccine; two patients died in spite of intensive therapy. There is now good evidence for giving prophylactic penicillin to asplenic patients but the efficacy of the pneumococcal vaccine remains uncertain.
4-Hz oscillations synchronize prefrontal–amygdala circuits during fear behavior
Authors: Nikolaos Karalis, Cyril Dejean, Fabrice Chaudun, Suzana Khoder, Robert R Rozeske, Hélène Wurtz, Sophie Bagur, Karim Benchenane, Anton Sirota, Julien Courtin, Cyril Herry
Journal: Nature Neuroscience (2016)
Novel method for predicting chemoresistance to paclitaxel in epithelial ovarian cancer patients
Authors: D. Silasi, T. J. Rutherford, P. E. Schwartz, R. Chen, A. Alvero, I. Visintin, G. Mor
Journal: Journal of Clinical Oncology (2006)

15007 Background: No available test exists to guide the selection of effective chemotherapeutic regimen in recurrent ovarian cancer. Preliminary studies in our lab have identified a protein, MyD88, a major component in the inflammatory pathway, to be highly expressed in epithelial ovarian cancer cells that exhibit primary or acquired Paclitaxel chemoresistance. The objective of this study was to develop a sensitive approach that can detect expression of MyD88 in ovarian cancer tissue. We report the development of a test based on Laser capture microdissection that allows detection of MyD88 in a 6000 cell sample. Methods: Tumor tissue was obtained at surgery from epithelial ovarian cancer patients and snap-frozen in liquid nitrogen. Eight micron sections were prepared on polyethylene covered glass slides and tumor cells were dissected with a Laser capture microdissection system. Protein expression was detected by Western blot analysis. Results: Protein expression was detected by Western blot analysis in 1000 microdissected cells. An inverse correlation was observed between MyD88 expression in tumor cells and clinical response to Paclitaxel. Furthermore, this method allows the isolation of CD-45 positive cells from the tumor and analysis of their protein expression. Conclusions: We describe for the first time a method that will allow us to predict chemoresistance. Laser capture microdissection is a powerful technique that can be used to study the protein profile of each of the cellular components present in the tumor microenvironment. This technique will facilitate our understanding of the proteins necessary for tumor growth and may help to identify novel markers or potential protein targets. No significant financial relationships to disclose.
Murder and assault arrests of White House cases: clinical and demographic correlates of violence subsequent to civil commitment
Authors: D Shore, C R Filson, W E Johnson, D S Rae, P Muehrer, D J Kelley, T S Davis, I N Waldman, R J Wyatt
Journal: American Journal of Psychiatry (1989)

The authors studied arrest records and clinical data on 217 persons formerly hospitalized as "White House Cases" because they were psychotically preoccupied with prominent political figures. Prior arrest for violent crime was the variable most strongly associated with arrest for violent crime after hospital discharge. Male gender and a history of weapons possession were also correlated with future violence. For those with prior violent crime arrests, hospital incidents requiring seclusion were also associated with later violence. For those without prior arrests, subsequent violence was associated with threats, living outside Washington, and command hallucinations. For those previously arrested for nonviolent crimes, only persecutory delusions were associated with later violence.
Abstract 15264: Additional Value of Cardiac Computed Tomogragraphy to Assess Prosthetic Valvular Dysfunctions
Authors: Nataliya Hrynchyshyn, Arshid Azarine, Alireza Samadi, Ludivine Perdrix, Rabea Khedim-Touati, Elie Mousseaux, Benoit Diebold
Journal: Circulation (2012)
A New BCR-ABL1 Mutation (L248R) Is Highly Resistant to Imatinib, Bosutinib, Nilotinib and Dasatinib, but Can Be Inhibited by AP-24534 and DCC-2036.
Authors: Sara Redaelli, Luca Mologni, Roberta Rostagno, Rocco Piazza, Michela Viltadi, Scott Wise, Daniel Flynn, Carlo Gambacorti-Passerini
Journal: Blood (2010)
Positron emission tomography response evaluation from a randomized phase III trial of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone for patients with metastatic adenocarcinoma of the pancreas
Authors: R.K. Ramanathan, D. Goldstein, R.L. Korn, F. Arena, M. Moore, S. Siena, L. Teixeira, J. Tabernero, J.-L. Van Laethem, H. Liu, D. McGovern, B. Lu, D.D. Von Hoff
Journal: Annals of Oncology (2016)

In the phase III MPACT trial, nab-paclitaxel plus gemcitabine (nab-P + Gem) demonstrated superior efficacy versus Gem alone for patients with metastatic pancreatic cancer. We sought to examine the feasibility of positron emission tomography (PET) and to compare metabolic response rates and associated correlations with efficacy in the MPACT trial.
In situ evaluation of residual breast tumor and tumor grade using medical hyperspectral imaging (MHSI)
Authors: J. E. Freeman, S. Yang, S. V. Panasyuk, R. A. Lew, D. Ngo, D. V. Faller, A. E. Rogers
Journal: Journal of Clinical Oncology (2006)

10677 Background: MHSI is a camera-based technique providing spectral data regarding tissue chemistry for each pixel in an image. Over 30% of women suffer local recurrence after resection. Intraoperative assessment of residual tumor &amp; tumor grade would optimize care. Methods: We studied 42 S-D rats w/ breast tumors induced by gavage of DMBA &amp; 15 controls. Tumors were exposed &amp; resected, intentionally leaving ∼1mm residual tumor pieces. Gross examination, histo-pathology &amp; MHSI (total 335) were performed for tumors, tumor beds after partial and total resection &amp; control sites. A visible light MHSI system (HyperMed,Waltham, MA) w/ 40μm resolution &amp; algorithms based on spectral features of the surgical field were developed and implemented for this study. Gross observation at surgery represents truth, as small tumor pieces were left intentionally by the surgeon and recorded. Samples from tumor beds were collected and histopathologically analyzed. When seen, gross tumor was removed from tumor bed by the pathologist. Results: MHSI performed well at identifying tumor. The kappa statistic(κ) for gross vs MHSI (84%) is significantly higher than κ for gross vs histopathology (76%) where for the κ the estimated asymptotic standard error is 3%. MHSI associates more strongly with gross than histopathology does. 81 tissue samples were separated into histologic grade: 0 = normal, 1 = benign tumor, 2 = intraductal Ca, 3 = papillary &amp; cribiform Ca, 4 = papillary &amp; cribiform Ca with invasion &amp;/or comedo Ca. The imaging team (blinded) assigned tumor grade to each MHSI image. Statistical analysis defined 3 histologic groups: 9 normal (grade 0) tissue, 18 benign &amp; intraductal tumors (grades 1–2), 54 advanced tumors (papillary, cribiform with invasion/comedo Ca, grades 3–4). Both histopathology &amp; MHSI identified all 9 normal samples. Of 18 samples in group 2 (benign/intraductal by histopathology), 17 were qualified as benign/intraductal by MHSI (94% sens) &amp; 1 as advanced. Of 54 samples with adv tumors by histopathology, MHSI identified 48 (89% sens) as advanced &amp; 6 as intraductal. Conclusions: MHSI may provide convenient intraoperative, near real-time images with useful data about residual tumor &amp; tumor grade. Human trials are planned. [Table: see text]
Treatment of patients with gestational trophoblastic neoplasia (GTN) in 12 South America referral centers: Results after 10 years since international FIGO consensus.
Authors: Gustavo Jankilevich, Elza Uberti, Antonio Braga, Maria Ines Bianconi, Izildinha Maesta, Mauricio Viggiano, Sue Sun, Rafael Cortes Charry, Aleydah Salazar, Bruno Maurizio Grillo, Juandyr Moreira de Andrade, Eduardo Silveira, Jose Mauro Madi, Lourdes Rodriguez, Silvina Otero, Jorge de Rezende-Filho, Maria Do Carmo Fajardo, Joffre Amim-Junior, Sergio Lunardon Padilha
Journal: Journal of Clinical Oncology (2014)

e16508 Background: GTN is a curable disease. The quality of care following international guidelines and multidisciplinary dedicated teams are cornerstones to achieve successful results. Reports from South America are rare. We report results with patients (pts) with GTN according to disease progression and FIGO staging, survival, pathological diagnosis of previous gestation and adherence to follow-up. Methods: We reviewed medical records and data bases from twelve referral centers in South America. Cohort patients were treated between January 2000 and December 2011. Results: Gestational Trophoblastic Disease was diagnosed in 5,771 pts. Mostly were brazilian origin (86%) and other countries 14%. Spontaneous remission were reported in 4,438 pts (76.9%) and 1,333 pts (23.1%) were diagnosed as GTN. In the GTN group initial pathological results of previous gestation were complete Hydatidiform Mole (HM) in 971 cases, partial HM in 125 cases, choriocarcinoma in 131 pts, another histopathological diagnosis in 37 cases, and 51 pts had no pathological results. According to the FIGO/WHO staging, 963 (72.2%) patients were in Stage I; 67 (5.0%) Stage II; 268 (20.1%) Stage III and 35 (2.6%) Stage IV. All pts were scored: 1,069 cases (80.2%) as low-risk GTN and 246 (18.5%) as high-risk GTN. Eighteen pts 18 (1.4%) had placental site trophoblastic tumor (PSTT). The cure was achieved in 95,6% of the pts in the intent to treat group; 99,6% in low risk GTN, 89,4% in high risk, without differences between countries. In the setting of PSTT the overall survival was 83,3%. Adherence to treatment and suggested follow-up was high in GTN: 1,157 of 1303 patients (88.8%) completed the follow-up. Conclusions: This is the biggest report on GTN from South America. Results showed high rate of long term remissions following international guidelines across the continent with social and economic disparities. Patients with molar gestations should be referred to a referral centers for an early diagnosis and treatment of GTN.
Survey of cetuximab activity in irinotecan-refractory metastatic colorectal cancer patients
Authors: P. Afchain, J. B. Bachet, T. André, B. Landi, E. Mitry, C. Tournigand, C. Lepère, C. Louvet, J. N. Vaillant, P. Rougier
Journal: Journal of Clinical Oncology (2006)

13533 Background: The BOND study demonstrated Cetuximab (Cx) activity in irinotecan-refractory metastatic colorectal cancer (IRMCCR) patients (pts). Cx was approved in Europe early 2004 for this population. The aim of this study was to survey its efficacy in a unselected population of IRMCCR treated in 4 french academic centers. Methods: Data of all IRMCCR pts who had received Cx with or without irinotecan regimen between Jan 2004 and Sept 2005 were included in this survey. Exhaustivity of treated pts was established based on pharmacy registry. Primary end-point was time to tumor progression (TTP). Secondary end-points were overall survival (OS) and tumor response (RECIST). Results: Characteristics of the 76 included IRMCCR pts were : male/female : 44/32; median age 59.5 yrs (range 23 - 79); performance status : 0–1 (59 pts) and 2–3 (17); median number of tumor sites : 2 (1 - 5). The median number of chemotherapy regimens preceeding first Cx administration was 3 (range 1 to 5). At least one local treatment of the metastases (surgical resection and/or radiofrequency ablation) was a part of the strategy before Cx for 39 pts (51.3%). EGFR status was positive in 72 pts and negative in 4. Cx was administered : alone in 4 pts, combined with FOLFIRI in 4 and with irinotecan alone in 68 (89%). 10 pts received only one infusion Cx (early clinical progression : 6; patient decision : 2; early death : 2). Median number of Cx infusions was 10 (range 1 to 60). Median TTP (intent-to-treat) was 3.3 months [IC95% : 2.2–4.6]. Median OS since first-line chemotherapy and first Cx administration were 33.6 months [IC95% : 27.7–41.1] and 7.6 months [IC95% : 5.6–9.5], respectively. Tumor response (full population) was complete response 1.3%, partial response 19.7% (overall response 21%), stable disease 25% (disease control : 46%), progression 37% and not evaluable 17%. Conclusions: This therapeutic survey in a unselected population of IRMCCR are in accordance with the results of the BOND study for TTP, OS and tumor response. (supported by ADEBIOPHARM ER48). [Table: see text]
Multicenter phase II study of irinotecan plus weekly bolus 5-FU and high dose <b><i>l</i></b>-leucovorin for patients with metastatic colorectal cancer (OGSG 0201)
Authors: H. Ishida, H. Mishima, S. Iwamoto, T. Morimoto, T. Kato, T. Tsujinaka, H. Furukawa
Journal: Journal of Clinical Oncology (2004)

3718
Evaluation of the CpG island methylator phenotype as a predictive biomarker for adjuvant oxaliplatin-based chemotherapy in colorectal cancer.
Authors: Stacey Shiovitz, Chen Wu, Ming Yu, Georgia Gourgioti, Georgia Raptou, Vassiliki Kotoula, George E. Pentheroudakis, Konstantine T. Kalogeras, George Fountzilas, William M. Grady
Journal: Journal of Clinical Oncology (2015)

592 Background: The CpG island methylator phenotype (CIMP) has previously been shown to be a predictive biomarker for 5-fluorouracil (5-FU)/leucovorin (LV)/irinotecan (IFL) adjuvant chemotherapy in stage III colon cancer patients. It is unknown if CIMP serves as a biomarker for standard-of-care oxaliplatin-based adjuvant therapy. Methods: HE6C05 randomized 441 patients with stage II/III colorectal adenocarcinoma to adjuvant oxaliplatin with either capecitabine (XELOX) or 5-FU/LV (mFOLFOX6) between November 2005 and January 2008. The primary objective was disease-free survival (DFS); overall survival (OS) was a secondary objective. The study closed early due to poor accrual with last follow-up in November 2013. Isolated DNA from 293 tumor samples was used to determine CIMP status based on methylation patterns at the CACNA1G, IGF2, NEUROG1, RUNX3, and SOCS1 loci. Cox univariate and multivariate models were used to assess the effects of CIMP on DFS and OS, accounting for interactions with TNM stage; site (right vs. left); KRAS, BRAF, and mismatch repair (MMR) status; tumor T-cell ratio (CD3/CD8); and treatment arm. Results: Of the tumor samples available for CIMP analysis, 28 (9.6%) were CIMP-positive. The CIMP-positive tumors were more likely to be right-sided and have BRAF mutations (chi-square, p&lt;0.001). In the univariate analysis, no significant differences in DFS or OS were observed between individuals with CIMP-positive vs. negative tumors (OS hazard ratio 1.27, Wald’s p=0.55). In addition, CIMP had no predictive value for response to the treatments administered in the two arms of the trial (XELOX vs. mFOLFOX6). In the multivariate model, only TNM stage and primary site were associated with survival outcome (Wald’s p=0.0002 and p=0.006, respectively); CIMP did not improve treatment response prediction. Conclusions: In this exploratory analysis, unlike what we have seen with IFL, CIMP does not appear to serve as a predictive biomarker for treatment response to oxaliplatin-based therapy. CIMP analysis in an irinotecan vs. oxaliplatin trial may offer additional insight.
A pilot study of external beam radiotherapy for unresectable primary liver cancer
Authors: J. Furuse, H. Ishii, M. Kawashima, M. Nagase, T. Ogino, M. Yoshino
Journal: Journal of Clinical Oncology (2004)

4220 Background: Radiotherapy is used to treat patients with unresectable primary liver cancer, including intrahepatic cholangiocarcinoma (IHC) and hepatocellular carcinoma (HCC), but the efficacy has never been examined well. The purpose of this study was to clarify the efficacy and feasibility of external beam radiotherapy (EBRT) alone in such patients. Methods: Twenty-one patients with unresectable primary liver cancer, 11 with IHC and 10 with HCC were enrolled in this prospective trial between June 1998 and August 2003. The eligibility criteria were: clinical target volume that encompassed gross tumor volume plus lateral margin of 1 to 2 cm can receive more than 95% of prescribed dose; no distant metastasis; performance status 0, 1 or 2; Child-Pugh classification A or B; no massive ascites or pleural effusion; no serious complications; and written informed consent of the patient. We performed EBRT (50 Gy in 25 fractions, 5 times/week) and evaluated its efficacy and adverse effects during a 3- to 34-months follow-up period. Time to progression (TTP) and survival time (ST) were calculated by the Kaplan-Meier method from the date of starting radiotherapy. Results: The full irradiation dose was administered in 19 of 21 patients. Irradiation was discontinued after 8 Gy because of obstructive jaundice in 1 patient with IHC, and after 36 Gy because of massive ascites in 1 patient with HCC. Grade 3 or 4 toxicity was observed in 6 of the 21 patients (28.6%), i.e., 5 with HCC and one with IHC; ascites developed in all 6 of them and total-bilirubin elevation in 2 of them. There were no direct treatment-related deaths. Overall response rate (OR) in assessable 19 patients was 47% (95% CI, 27–68%), including 2 CR, 7PR, 8SD, and 2 PD. The OR of the HCC patients was 50% (2 CR, 3 PR, 4 SD, 2 PD), and the OR of the IHC patients was 44% (4 PR, 4 SD, 1 PD). The median TTP and ST of the 21 patients were 4.4 months and 9.9 months, respectively. The 1- and 3-year survival rates were 38% and 19%, respectively. Conclusions: Raidotherapy with 50 Gy was tolerated except for the development of ascites in HCC. It is effective against primary liver cancer and warrants further investigation to determine the survival benefit. No significant financial relationships to disclose.