tbuckley/cabot-search huggingface dataset:
Focal treatment of prostate cancer using Focal One device: Pilot study results.
Authors: Gilles Pasticier, Sebastien Crouzet, Olivier Rouviere, Jean-Yves Chapelon, Florence Mege-Lechevallier, Xavier Martin, Albert Gelet
Journal: Journal of Clinical Oncology (2015)

112 Background: To evaluate the efficacy of Focal One device for focal treatment of localized prostate cancer. Methods: Focal One is a device designed for the focal therapy of Prostate Cancer integrating the ability to visualize, target, treat and validate the focal treatment. Magnetic Resonnance Imaging (MRI) volumes are imported through the hospital’s network into the device so that an elastic fusion can be done between the real time ultrasonography and the MRI where the regions to treat have been previousy drawn, thus allowing to apply limited and targeted HIFU lesions. During the HIFU energy delivery process, the operator sees a live ultrasound image of what is being treated and, if necessary, can readjust the treatment planning. At the end of the treatment process, a Contrast-enhanced Ultrasound volume is acquired showing the de-vascularized areas. Ten patients with mono focal prostate cancer were treated between march 2013 and January 2014.HIFU treatment process was realized with the Focal One device using a 6 mm safety margin around the tumor. Contrast enhanced MRI is performed at day 2 after HIFU and Control biopsies guided with contrast-enhanced Ultrasound imaging were achieved one month after HIFU inside and in the rime of the treated area. Results: The mean age of patients was 65.8±5.5 years. The Clinical stage was T1for 9 patients and T2afor 1patient.The Gleason sum was 6 for 7 patients and 7(3+4) for 3 patients. The PSA value was 4.47± 3.7 ng/ml and the mean Prostate Volume was 50±23 cc .The mean treated volume was 14 cc (7.3-20.4) 28% of prostate gland. The mean nadir PSA value was 3.46±2 ng/ml. In all patients, targeted biopsies inside the treated area performed day 30 after the HIFU session demonstrated a complete destruction of the targeted tumor. No Incontinence was observed .A partial loss of potency (IIEF &lt;17) occurred in 2 patients. Conclusions: Focal One device is able to achieve a complete destruction of small prostate cancer using an elastic magnetic resonance-ultrasound (MR-US) registration system for tumor location and HIFU treatment planning. Multicenter trial is in progress (30 patients).
Using a new patient process to improve breast care access.
Authors: Eleanor Miller, Jonathan Colon, Nancy O'Connor
Journal: Journal of Clinical Oncology (2013)

171 Background: Access to timely care is of major focus in oncology. Clinicians and administration collaborated to improve the training and support for non medical staff involved in the new patient process at the breast center. The goal of the process was to improve upon the surgical triage of patient appointments for those with suspicious mammograms or newly diagnosed with breast cancer in less than one week, use the nurse practitioner clinics most effectively, and to triage other diagnoses and patients per updated guidelines, thereby increasing access to care. Methods: A new patient intake form was created with the assistance of IT and added to the electronic medical record as a tool for use by clinical and nonclinical staff. Clinicians and administration also met to update the new patient process forming a decision tree, which ultimately was developed into a manual. A series of in-services were held with scheduling and clinical staff for education and training. Education was also provided to refer patients with complex needs to the nurse navigator. Outcomes were measured by clinical and administrative staff. Results: Access to surgery clinics has improved for new breast patients since the process updates were implemented. Patients can be seen an average of 3.5 days sooner for both malignant and benign diagnoses. Access to the nurse practitioner clinic also improved by 9.4 days. Patients that are diagnosed within the health system can be seen within 3 days, and those that are diagnosed outside the system, within 7 days. Conclusions: It was the goal to improve access to the breast center by updating the intake and scheduling guidelines to see patients with a new diagnosis of breast cancer or other breast problems more quickly. Having guidelines that can be followed by clinical and non clinical staff promotes communication and collaboration, as well as a consistent approach among staff. In the future, the continued refinement of the new patient process and ongoing collaboration will further improve access to care.
The cost-effectiveness of bevacizumab in combination with paclitaxel in first-line treatment of patients with metastatic breast cancer.
Authors: A. J. Montero, S. Gluck, G. d. L. Lopes
Journal: Journal of Clinical Oncology (2011)

6060 Background: Bevacizumab in combination with chemotherapy increases progression-free survival (PFS) but not overall survival (OS) when compared to chemotherapy alone in the treatment of metastatic breast cancer (MBC). Recently, the United States Food and Drug Administration announced it would withdraw its approval of bevacizumab in breast cancer because its benefits did not outweigh its “significant risks”. The European Medicines Agency, in contrast, maintained its approval of bevacizumab in combination with paclitaxel, but not with docetaxel or capecitabine. While neither agency considers health economics in their decision-making process, one of the greatest challenges in the practice of oncology today is to reconcile hard-won small incremental clinical benefits with exponentially rising costs. Methods: In order to inform policy-makers in the US, this study aimed to assess the cost-effectiveness of bevacizumab plus paclitaxel in MBC, from a payer perspective. We created a decision-analytical model using efficacy and adverse events data from the ECOG 2100 trial. Health utilities were derived from available literature. Costs were obtained from the Center for Medicare Services Drug Payment Table and Physician Fee Schedule and are represented in 2010 US dollars. Quality-adjusted life years (QALY) and Incremental Cost Effectiveness Ratio (ICER) were calculated. Sensitivity analyses were performed. Results: Bevacizumab added 0.49 years of PFS and 0.135 QALY with an incremental cost of $100,300 and therefore a cost of $204,000 per year of PFS gained and an ICER of $745,000 per QALY. The main drivers of the model were drug acquisition cost, PFS, and health utility values. Using a threshold of $150,000/QALY, drug price would have to be reduced by nearly 80% or alternatively PFS increased by 10 months to make bevacizumab cost-effective. The results of the model were robust in sensitivity analyses. Conclusions: The addition of Bevacizumab to paclitaxel is not cost-effective in the treatment of metastatic breast cancer. Value-based pricing and the development of biomarkers to improve patient selection are needed to better define the role of the drug in this population.
Changes in Regional Oxygenation At the Site of Sickle Cell Vaso-Occlusive Pain
Authors: Roberta Miyeko Kato, Anne Nord, Erin McGuire, Daniel Gardner, Adam M Bush, Jon Detterich, Michael Khoo, Herbert J Meiselman, John C Wood, Vasilios Berdoukas, Thomas D. Coates
Journal: Blood (2012)
Blockage of CGEN-928 Expression Down-Regulates AKT Signaling Pathway and Inhibits Multiple Myeloma (MM) Cell Proliferation
Authors: Haiming Chen, Mingjie Li, Jennifer Li, Marissa P Dreyer, Cameryn P Ahles, Tiffany Lee, Joleen T Qiu, Cathy Wang, Eric Sanchez, Benjamin Bonavida, Ofer Levy, Liat Dassa, Gady Cojocaru, Zurit Levine, James R. Berenson
Journal: Blood (2011)
Gene-expression signatures as prognostic for relapse in stage I testicular germ cell tumors (TGCT).
Authors: Jeremy Howard Lewin, Philippe L. Bedard, Robert James Hamilton, Peter W. M. Chung, Malcolm J. Moore, Michael A.S. Jewett, Lynn Anson-Cartwright, Carl Virtanen, Neil Winegarden, Benjamin Haibe-Kains, Padraig Richard Warde, Joan Sweet, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2016)

493 Background: Genomic signatures may compliment pathological features in identifying appropriate patients who may benefit from adjuvant therapy in Stage I (SI) TGCT. This study aimed to identify a gene expression pattern to differentiate between relapsed (R) and non-relapsed (NR) SI TGCT. Methods: Patients with SI non-seminoma (NS) and seminoma (S) were identified from an institutional database from 2000 to 2012. All patients were managed with active surveillance. NR-NS and NR-S patients were defined as having no evidence of relapse after 2 and 3 years of surveillance respectively. Following pathology review, RNA extraction and gene expression analysis was performed on archived paraffin embedded tumor and normal testicular tissue using Illumina Whole Genome DASL Human HT-12 V4 BeadChip. Hierarchical clustering analysis, ANOVA and t-tests were used to evaluate candidate genes and expression patterns that could differentiate NR and R samples. Results: 57 patients (12 R-NS, 15 R-S, 15 NR-NS, 15 NR-S) were identified with median relapse time of 5.6 (2.5-18.1) and 19.3 (4.7-65.3) months in NS and S cohorts respectively. 3 additional normal testis samples were included. Poor prognostic factors were more frequent in R versus NR cases (NS: vascular invasion [5/12 vs 0/15]; S: median size [4cm vs 2.8cm]). Unsupervised hierarchical clustering of 22822 probes randomly separated S from NS, indicating no batch effect. One-way ANOVA revealed 4525 significantly varying probes (p &lt; 0.05) however, no statistically significant gene expression profile differentiated the 4 cohorts. A discriminative gene expression profile between R and NR cases was discovered when combining NS and S samples using 10 (p = 0.03) and 30 (p = 0.03) probe signatures with a 10 fold cross-validation. However, this profile was not observed in the S and NS cohorts individually. Conclusions: A discriminating signature for R and NR was identified for SI testis tumors, but not separately for NS and S. Biological relevance of these signatures is to be determined. Further studies are required to corroborate this profile in NS and S. If validated, these expression patterns could help identify patients beyond standard pathological risk algorithms for optimal management.
Analysis of response to methylnaltrexone by response to previous dose in advanced illness patients with opioid-induced constipation
Authors: J. Thomas, W. Wang, N. Yan, C. Su, R. Lynn, N. Stambler, R. Israel
Journal: Journal of Clinical Oncology (2008)

9626 Background: Methylnaltrexone is a selective mu-opioid receptor antagonist that blocks peripheral opioid side effects without affecting central analgesia. A 2-week QOD subcutaneous (SC) dosing study in advanced illness patients with opioid-induced constipation (OIC) showed that significantly more patients treated with methylnaltrexone (48.4%; n=62) than placebo (15.5%; n=71) had a laxation response within 4 hours after the first double-blind dose (DDW 2006). Methods: This subanalysis compared the clinical response (rescue-free laxation within 4 hours post-dosing) between methylnaltrexone and placebo by clinical response to previous doses during the 7 doses of the double-blind phase. All patients who had all doses up to the dose being analyzed were included in the analyses. Two-sided Fisher’s exact test was used to compare response rates between methylnaltrexone and placebo. Results: Of patients who failed to respond to the first dose, 34% and 9% responded to the second dose of methylnaltrexone or placebo, respectively (p=0.006). Of those who failed to respond to the first 2 doses, 26% and 12% responded to the third dose of methylnaltrexone or placebo, respectively (p=0.16). Of patients who did not respond to the first 3 doses, 7% and 8% responded to the fourth dose of methylnaltrexone or placebo, respectively. For each of the doses 2 to 7, the response rate among patients who had responses to all previous doses ranged from 57% to 100% in the methylnaltrexone group vs 0% to 11% in the placebo group. For doses 3 to 7 in patients with only 1 non-laxation response to previous doses, the likelihood of responding to the next dose was 38% to 67% for methylnaltrexone and 0% to 9% for placebo. Conclusions: 57% to 100% of patients who responded to all prior doses continued to respond to subsequent SC methylnaltrexone treatment at QOD dosing over 2 weeks, indicating a predictable and sustainable response. For those failing to respond to the first dose or possibly the first 2 doses, more patients responded to methylnaltrexone than placebo on the subsequent dose. However, these data suggest that patients who failed to respond to the first 3 consecutive doses were unlikely to respond to subsequent doses. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Progenics Pharmaceuticals, Inc., Wyeth Pharmaceuticals Wyeth Pharmaceuticals Progenics Pharmaceuticals, Inc., Wyeth Pharmaceuticals Progenics Pharmaceuticals, Wyeth Pharmaceuticals Wyeth Pharmaceuticals
Age-dependent effects of intensive chemotherapy (IC) on quality of life (QOL) and physical function in patients with acute myeloid leukemia (AML).
Authors: H. Z. Mohamedali, H. Breunis, J. Brandwein, M. Li, N. Timilshina, M. Minden, G. A. Tomlinson, S. M. H. Alibhai
Journal: Journal of Clinical Oncology (2011)

9088
Quantitative analysis of the impact of deepness of response on survival time following patients with metastatic colorectal cancer treated by chemotherapy and anti-EGFR monoclonal antibodies.
Authors: Hiroki Osumi, Satoshi Matsusaka, Mitsukuni Suenaga, Takeru Wakatsuki, Mariko Ogura, Masato Ozaka, Eiji Shinozaki, Keisho Chin, Nobuyuki Mizunuma
Journal: Journal of Clinical Oncology (2014)

493 Background: "Deepness of response" (DpR) is a new efficacy outcome measure that could explain the impact of tumor shrinkage on long-term survival outcome. In FIRE-3 trial, OS was significantly longer in patients (pts) treated with FOLFIR plus cetuximab compared with pts who received FOLFIRI plus bevacizumab. One reason was that first-line treatment with Cetximab have a DpR, so it takes a lot of time to grow tumors. The aim of the present analysis was to evaluate OS, PFS, pathological grade and DpR for pts with mCRC treated with anti EGFR antibody+FOLFOX or FOLFIRI. Methods: A total of 100 pts with histopathologically confirmed mCRC treated with first-line chemotherapy in combination with anti-EGFR antibody and second-line chemotherapy with cetximab were enrolled between October 2008 and June 2013. First, we compare DpR for pts with first-line chemotherapy+anti EGFR antibody and second-line chemotherapy+cetximab. Second, we analyzed DpR and pathological grade for 32 pts performed conversion surgery. Third, we compare OS, PFS and DpR for 43 pts treaded with second-line chemotherapy+Cetximab. Results: The 38 (26) pts treated with FOLFOX+cetximab (panitumumab) had a mean DpR of 44.9 (51.4)% (Interquartile range [IR]:36.6 (39.8)%, 60.97 (64.65)%), minimum DpR -45.2 (0)%. The 43 pts treated with second-line FOLFIRI + Cetximab had a mean DpR of 10% (IR:-7.8%, 30.9%) and a minimum DpR of -158%. The DpR wans’t different between first-line FOLFOX+cetximab and panitumumab. But the DpR was significantly different between first-line FOLFOX+cetximab and second-line FOLFIRI+cetximab. Tumor regression grades 0 after preoperative. FOLFOX+cetximab (panitumumab) had a mean DpR of 61.3 (0)%, grade 1 had a mean DpR of 50.83 (56.14)%, grade 2 had a mean DpR of 54.91 (40.5)% and grade 3 had a mean DpR of 58.5 (76)%. Individual DpR of the pts treated with FOLFIRI+cetximab is a significant prognostic factor for survival time (OS and PFS) in the Longest diameter-based models (PFS:p=0.006 OS:p=0.01). Conclusions: Our results emphasize the value of the variable DpR as a new efficacy outcome measure and the DpR was shown to be associated with its ability to prolong OS and PFS.
Correlation between pancreatic tumor size as measured on 3D CT scan versus pathologic specimen: Impact on radiation treatment volume.
Authors: H. Qiu, C. C. Hsu, E. K. Fishman, R. Tuli, C. L. Wolfgang, B. H. Edil, R. H. Hruban, L. Zheng, D. Laheru, J. M. Herman
Journal: Journal of Clinical Oncology (2011)

276 Background: Definition of the target volume for irradiation of pancreatic cancer (PCA) must balance coverage of micrometastatic disease with toxicity. To determine differences between radiographically defined tumors and true pathologic tumor specimens, we correlated the maximum tumor diameter (TD) of preoperatively imaged tumors with resected tumor specimens. Methods: With IRB approval, a retrospective chart review of patients who underwent resection of PCA between 2006 and 2010 was conducted. 73 patients were identified with preoperative CT imaging and pathologic analysis of tumors. 70 of 73 patients had a preoperative 3D CT performed. The TD as measured by a radiologist (EF) on contrast CT and 3D CT reconstruction was compared with that measured by pathological analysis of the resected specimen. Results: 70 patients underwent resection with preoperative CT imaging; 14.1% of these patients had CT performed &gt;6 weeks prior to surgery. The mean (SD) pathologic maximum TD was 31.3 mm (11.3) with range 3 mm to 60 mm. Whereas TD was underestimated by 1.9 mm (1.7 SE) with CT relative to pathologic analysis, this difference was not statistically significant (paired t-test, p=0.27) with a correlation coefficient of 0.265. 3D CT imaging had a smaller mean difference with a mean 3D CT diameter 0.4 mm (1.76 SE) larger than the pathologic specimen (p=0.82) with correlation coefficient 0.222. However, the max TD on 3D CT imaging was on average 2.3 mm larger than on CT (p=0.016) with correlation coefficient 0.798. Of patients with R0 resections (N=48), CT underestimated path size by 3.1 mm (p=0.020), whereas 3D CT was slightly larger (0.1 mm, p=0.949). For R1 resections (n=22), both CT and 3D CT overestimated size (0.8 mm and 1.1 mm, respectively, p&gt;0.5). Conclusions: PCA TD is generally underestimated on CT imaging, yet better approximated with 3D CT. Improved correlation was seen between CT and pathologic specimens following R0 resection. Alternatively, R1 resection specimens were slightly overestimated by CT/3D CT imaging. As a result, clinical target volumes should be expanded accordingly during radiotherapy planning to properly account for these discrepancies in the gross tumor. No significant financial relationships to disclose.
Detection and genomic interrogation of circulating tumor cells (CTCs) and circulating tumor stem cells (CTSCs) from men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Terence W. Friedlander, Vy Ngo, Shaun Doty, Qiang Zhao, Huang Dong, Charles J. Ryan, Wen-Tien Chen, Pamela Paris
Journal: Journal of Clinical Oncology (2013)

144 Background: Isolation, enumeration, and genomic profiling of CRPC CTCs offers the potential to discover genetic changes that occur in advanced disease. The Vitatex VitaCap platform captures CTCs based on their ability to invade collagenous matrices (CAM), allows for CTC and CTSC capture independent of EpCAM status, and yields viable cells suitable for comprehensive genomic analysis. In this study we sought to compare CTC yields between the VitaCap and the Veridex CellSearch platforms, to determine the utility of prostate-specific membrane antigen (PSMA) as a mCRPC CTC biomarker, to identify CTSCs and CTC clusters, and to explore the feasibility of CTC epigenomic analysis. Methods: CTCs were isolated and enumerated simultaneously using the CellSearch and VitaCap platforms in 23 men. CAM isolated CTCs and CTSCs were defined as EpCAM+PSMA+ and CD44+DPPA5+ respectively, and were enumerated immunocytochemically (ICC) and by flow cytometry. CTC clusters were enumerated by ICC. The Illumina HumanMethylation27 BeadChip was used to determine whole genome methylation status for CAM isolated cells. Results: 35 samples were collected for CAM analysis. A median of 27 (range 0-800) and 23 (range 2-390) CAM+ CTCs/ml were detected by ICC and flow respectively. In a subset of 20 samples, a median of 7 CTCs/ml (range 0-85) were detected by the CellSearch platform. CTCs were detectable by either CAM or CellSearch in &gt;95% of samples. CAM isolated CTC clusters were observed in 23% of samples with a median 7 clusters/ml (range 1-200). CTSCs were detected in 70% and 97% of samples by ICC and flow respectively, with a median of 9 CTSCs/ml (range 1-264) by flow. The CTC methylation profile highly resembled mCRPC with hypermethylation occurring more frequently in pathways associated with apoptosis (p&lt;0.006), angiogenesis (p&lt;0.007), and VEGF signaling (p&lt;0.003). Conclusions: CAM and CellSearch platforms yield comparable CTC counts. CTSCs and CTC clusters are detectable using the CAM platform, and the CTC methylome closely resembles that of mCRPC. Correlation with clinical data may yield further insight into the functional significance of these findings.
Impact of neoadjuvant therapy on histopathologic response and survival in patients with primary high-grade retroperitoneal soft tissue sarcomas
Authors: T. R. Donahue, M. W. Kattan, S. D. Nelson, W. D. Tap, F. R. Eilber, F. C. Eilber
Journal: Journal of Clinical Oncology (2008)

10510 Background: The outcome of patients with primary high-grade retroperitoneal soft tissue sarcomas (RPS) is poor with a 5- year disease specific survival (DSS) of <40%. Surgical resection alone remains the current standard therapy. The impact of neoadjuvant therapy on histopathologic response and DSS are unknown. Methods: From 1987 to 2007, 55 patients with primary high-grade RPS received protocol neoadjuvant therapy (chemotherapy ± radiation). All patients underwent surgical resection and response was assessed histopathologically. Patients with ≥95% pathologic necrosis were classified as responders. Clinicopathologic variables were analyzed for DSS and compared to the Memorial Sloan-Kettering Cancer Center (MSKCC) Sarcoma Nomogram prediction for such variables. Tumor size was defined by cross-sectional imaging prior to treatment. Results: The median tumor size was 15 cm, and the median follow-up time for survivors was 68 months. The 5-year DSS for all 55 patients was 47% as compared to 37% predicted by the Sarcoma Nomogram. Fourteen (25%) of the patients had ≥95% pathologic necrosis and were defined as histopathologic responders; forty-one (75%) were non- responders. The 5-year DSS for responders was 83%. This was significantly better than the 5-year DSS of 34% for non-responders (p=0.002) and appeared superior to the 39% predicted by the Sarcoma Nomogram. The 34% 5-year DSS for non-responders was essentially the same as the 35% predicted by the Sarcoma Nomogram. Conclusions: Histopathologic response to neoadjuvant therapy in patients with primary high-grade retroperitoneal soft tissue sarcomas is associated with an improved DSS compared to non-responders and the Sarcoma Nomogram prediction. No significant financial relationships to disclose.
Prognostic Significance of Time to Relapse in Pediatric AML: Results from the International Randomised Phase III Study Relapsed AML 2001/01
Authors: G.J.L. Kaspers, M. Zimmermann, D. Reinhardt, B. Gibson, R. Tamminga, H. Armendariz, M. Dworzak, S. Ha, L. Hovi, A. Maschan, A. Baruchel, Y. Bertrand, B. Razzouk, C. Rizzari, P. Smisek, O. Smith, B. Stark, U. Creutzig
Journal: Blood (2008)