tbuckley/cabot-search huggingface dataset:
Prognostic significance of systematic pelvic and paraaortic lymphadenectomy (SLA) in apparent stage I epithelial ovarian carcinoma (EOC)
Authors: Y. Shimizu, F. Murakami, N. Ogawa, A. Yamazaki, T. Ishiya, S. Sakurai, K. Hasumi, S. Umezawa
Journal: Journal of Clinical Oncology (2008)

16502 Background: To assess the prognostic significance of SLA up to the upper level of renal vessels in apparent stage I EOC. Methods: Between 1/90 and 12/04, 250 consecutive patients (pts) with apparent stage I EOC received SLA in addition to hysterectomy, bilateral adnectomy, omentectomy with more extensive surgery including intestinal resections. Six cycles of cisplatin-based chemotherapy were given in pts with stage IB to IV EOC and at least 3 cycles given in pts with grade 2 or 3 stage IA. Results: Of 250 pts with apparent stage I EOC, 46 pts (18.4%) were upstaged to IIA (4), IIB (8), IIC (27), and IIIA (7) with abdominal staging. Retroperitoneal staging with SLA upstaged 54 pts (21.6%) of apparent stage I to IIIC. Totally, 79 pts (31.6%) were upstaged and the remaining 171 pts (68.4%) were found to have true stage I EOC. Thus, if the comprehensive surgery including SLA will not be done, 32% of apparent stage I EOC would be incorrectly under-staged. Lymph node (LN) involvement by pT1 subcategory was 8% in 96 pT1A pts, 56% in 11 pT1B, and 20% in 97 pT1C, respectively. Totally, 16% of 204 pT1 pts had LN involvement. Of 33 node-positive pts, 22 pts had positive paraaortic LNs without pelvic LN involvement, and paraaortic LNs were involved in 30 of the 33 node-positive pts. Multivariate analysis revealed tumor grade, substage, and endometrioid histology (favorable) were significant prognostic factor for LN involvement. Five-year survival was 98% for pT1N0M0 vs 75% for pT1N1M0 (p=0.0000). Five-yr survival was 93% for 204 pts with pT1 receiving SLA and 81% for pts with pT1 without SLA (p=0.0064), and it was 97% for SLA (+) vs 96% for SLA (−) in pts with pT1A, and 85% for SLA (+) vs 45% for SLA (−) (p=0.0029) in pts with pT1C, respectively. Conclusions: The present retrospective analyses demonstrated that SLA might bring a survival benefit in apparent stage I EOC. Thus, comprehensive surgical staging including SLA is valid for apparent stage I EOC in terms of both correct staging (diagnosis) and treatment (prognosis). No significant financial relationships to disclose.
Effect of metastatic site biopsy on circulating tumor cell (CTC) count in castrate resistant prostate cancer (CRPC) stage.
Authors: Manish Kohli, Patrick W Eiken, Brendan P McMenomy, Thomas D Atwell, Winston Tan, Rui Qin, Rachel Carlson, Michael B Campion, Liewei Wang, Brian Addis Costello, Henry Clement Pitot, Fernando Quevedo, Elizabeth A Scheel, Thai Huu Ho, Alan Haruo Bryce, Ricardo Paz-Fumagalli, Timothy J. Moynihan, Roxana Stefania Dronca, Minetta C. Liu
Journal: Journal of Clinical Oncology (2015)

190 Background: It is not known if biopsy of CRPC stage metastases alters CTC results. We evaluated pre &amp; post biopsy CTC counts in a prospective cohort undergoing pre-chemotherapy abiraterone acetate/prednisone (AA/P). Methods: CTC enumeration was performed on 7.5mL blood using the FDA cleared immunomagnetic/immunofluorescence assay (CellSearch). Time of blood draw for CTC counts pre/post biopsy was recorded for each biopsy. Biopsies were performed using 11/13 gauge core biopsy device for bone lesions and 18 gauge core needle biopsy device for soft tissue/nodal metastases. All patients (pts) underwent two serial biopsies 3 months apart. Change in CTC counts pre/post biopsy for visits 1 and 2 were evaluated using Wilcoxon signed rank test (significance at p&lt;0.05). Differences in CTC count change (visit1) pre/post biopsy based on metastatic site (skeletal vs. non-skeletal) was compared using Wilcoxon rank-sum test. Results: Median age of the cohort was 74 years (IQR: 68-78); median PSA at V1 was 16.4 ng/ml (IQR: 6.4-87.6); at V2 was 11.5 ng/ml (IQR: 1.8-23.7). Of 59 pts undergoing biopsies 42 were in bone and 17 in nodal/soft tissue masses. At V1, pre/post biopsy CTC counts were measured on 50 and 49 pts, respectively; at V2, pre/post CTC counts were measured on 43 and 36 pts. High volume metastatic disease at V1 was observed in 67.8 % of all pts. Table lists CTC counts and time of collection pre/post biopsy for both visits. Mean change in pre/post biopsy CTC counts for skeletal sites was 0.7 (range: -12 to 64) compared to 12.1 (range: -21 to 13) for non-skeletal sites (p=0.23). Conclusions: An increase in mean CTC counts after biopsy of CRPC metastases was observed. No significant differences in change of CTC counts based on site biopsied (skeletal versus non-skeletal) was noted. Correlation with clinical outcomes is on-going. Clinical trial information: NCT# 01953640. [Table: see text]
Association of In Vivo [<sup>18</sup>F]AV-1451 Tau PET Imaging Results With Cortical Atrophy and Symptoms in Typical and Atypical Alzheimer Disease
Authors: Chenjie Xia, Sara J. Makaretz, Christina Caso, Scott McGinnis, Stephen N. Gomperts, Jorge Sepulcre, Teresa Gomez-Isla, Bradley T. Hyman, Aaron Schultz, Neil Vasdev, Keith A. Johnson, Bradford C. Dickerson
Journal: JAMA Neurology (2017)

Previous postmortem studies have long demonstrated that neurofibrillary tangles made of hyperphosphorylated tau proteins are closely associated with Alzheimer disease clinical phenotype and neurodegeneration pattern. Validating these associations in vivo will lead to new diagnostic tools for Alzheimer disease and better understanding of its neurobiology.
High response rate to crizotinib in advanced, chemoresistant ALK+ lymphoma patients.
Authors: E. M. Pogliani, I. Dilda, F. Villa, F. Farina, G. Giudici, L. Guerra, A. Di Lelio, L. Borin, I. Casaroli, L. Verga, C. Gambacorti-Passerini
Journal: Journal of Clinical Oncology (2011)

e18507 Background: The Anaplastic Lymphoma Kinase (ALK) gene is fused to several partner genes (mainly NPM) in the majority of Anaplastic Large Cell lymphoma (ALCL) patients (pts). Deregulated ALK tyrosine kinase activity represents the oncogenic driver in this disease, through the phosphorylation of proteins involved in cellular proliferation, apoptosis and differentiation. Although ALK+ ALCL pts are responsive to cytotoxic drugs, relapses occur and bear a dismal prognosis. Crizotinib is an experimental competitive small-molecule inhibitor of the ALK and cMet/HGFR receptor tyrosine kinases with cellular IC50 values in NPM-ALK expressing cells comprised between 24 and 60 nM. A dose of 250 mg BID orally was previously established as the recommended dose in a phase I study. Methods: We report here on the safety and antitumor profile of crizotinib in 4 ALK+ lymphoma pts (age 20-26), resistant to cytotoxic therapy who received crizotinib 250 mg BID as part of a compassionate use named patient protocol. All pts were resistant to at least 3 lines of treatment, including autologous bone marrow transplantation (ABMT) in 2 cases. All pts had multiple sites of disease, an ECOG score of 3-4 and were symptomatic (fever, bone pain). No steroids or drugs with antineoplastic activity were allowed during crizotinib treatment. FISH analysis using an ALK break-apart probe was used to confirm diagnosis and to monitor BM aspirates. Disease status was also assessed by CAT/PET scans following RECIST criteria. Results: Disappearance of constitutional symptoms and LDH levels normalization were observed in all cases with median times of 5 and 25 days after crizotinib (range 2-10, 15-35 days) respectively. BM aspirates were positive for ALK+ cells in 3/4 cases (% of lymphoma cells: 3-65%): negativity was obtained in 3/3 cases after 1-2 months of treatment. The earliest sign of therapeutic activity visible by CAT/PET scan was observed at day 12. Three pts achieved a CR (8+, 5, 3+ months) and one a PR (2 months). The 2 relapsing pts had previously undergone ABMT. Toxicity consisted of transient G I-II diarrhea, rash and ocular flashes. Conclusions: Crizotinib exerts a potent antitumor acitivity in advanced ALK+ lymphoma pts demonstrating an ALK split gene.
The 2010 National Comprehensive Cancer Network (NCCN) research benchmarking survey (RBS): Clinical trials in the academic cancer center.
Authors: S. L. Sherman, M. B. Waldinger, D. E. Paul
Journal: Journal of Clinical Oncology (2011)

6116 Background: The 2010 NCCN RBS focused on therapeutic clinical trial volume, accrual rates, and protocol review processes at NCCN centers. The primary aim was to benchmark clinical trials activity including trial sponsorship, patient accrual, and the steps involved in protocol review. Methods: The survey collected quantitative and descriptive data on therapeutic trials, accruals, and sponsors. In addition, because the steps required for activation of clinical trials may result in delays and increase costs, the 2010 RBS focused on the processes and timeframes involved in protocol review. Results: Of newly reportable patients (105,917) from 19 centers reporting accruals over a 12-month period, 16,018 (15.1%) were recruited to therapeutic clinical trials; 6,097 trials (all phases) were reported. The average number of accruals per trial (all sponsors) was 2.63. 39% of trials (2,367) were sponsored by National Cancer Institute Cooperative Groups (NCI CGs), with 19% (2,866) of patient accruals attributed to NCI CG trials (1.21 accruals/trial). Comparatively, 22% of trials (1,364) were institutionally sponsored, while 40% of accruals (6,087) were enrolled in these trials (4.46 accruals/trial). 30% of trials (1,827) were industry sponsored (1,827), and accounted for 27% of accruals (4,016), or 2.20 per trial. Other peer-reviewed mechanisms accounted for the balance of trials and accruals. A broad range of timelines were reported for the steps involved in protocol review and activation indicating that 1) there are likely best practices that merit investigation and 2) further refinement and standardization of timeline definitions are warranted. An analysis of protocol review timelines is underway. Conclusions: Clinical research constitutes a core mission of NCCN centers. NCCN benchmarking efforts are undertaken to improve clinical trials operations and ultimately to impact the delivery of new therapies to patients. Accruals per trial for all sponsors appear low; the rate of 1.21 accruals per NCI CG trial is of particular concern. Further development of benchmarks and best practices will promote enhanced operations, timely review processes, and increased patient accrual.
Retrospective cohort study on the safety and efficacy of cetuximab for metastatic colorectal cancer patients: HGCSG0901—Analysis of predictive markers.
Authors: Kazuteru Hatanaka, Satoshi Yuki, Hiroshi Nakatsumi, Takahiro Kogawa, Hiraku Fukushima, Koshi Fujikawa, Yasushi Sato, Mayuko Saito, Masaki Munakata, Yoshito Komatsu
Journal: Journal of Clinical Oncology (2012)

683 Background: The anti-EGFR antibody Cetuximab (Cmab) do not provide therapeutic effect to patients with KRAS mutations. It has been reported that there is no correlation between the staining intensity of EGFR and efficacy of Cmab. Moreover, the previous studies have suggested that the intensity of skin toxicity that occurs after the administration is a predictive marker of Cmab. Methods: Of 269 cases registered in the multi-institutional retrospective study (HGCSG0901) treated with Cmab, 252 patients for 3rd line or after treatment line were analyzed. Each degree of skin toxicity, KRAS mutation status and EGFR expression status, respectively, were analyzed for response rates, progression-free survival (PFS) and overall survival (OS). The Response Evaluation in Solid Tumors (RECIST) criteria version 1.0 was used to assess tumor response. The Kaplan–Meier method was used to determine PFS and OS. Log-rank test was used to compare each regimen in terms of PFS and OS. All statistical tests were performed using SPSS. Results: KRAS status: wild type (WT)/mutant type (MT): 135/32, EGFR status: positive/negative: 210/38, Skin toxicity: Grade 0/1/2/3: 31/50/128/43. Analysis of KRAS status: Response rate: WT 23.7%/MT 6.3% (p=0.028), Progression-free survival: WT 4.8 months /MT 2.1 months (p&lt;0.001), Overall survival: WT 9.9 months/MT 5.3 months (p=0.003). There was a significant correlation between the degree of skin toxicity and efficacy. However, EGFR expression status showed no differences in efficacy. Conclusions: Here, we reported the results of efficacy analysis for each predictive marker of Cmab. As with previous reports, patients with KRAS mutations did not benefit from Cmab. Degree of skin toxicity was a useful indicator of effectiveness after starting treatment, whereas EGFR status was not effective predictor in daily practice setting.
Cisplatin and etoposide as first line treatment in adult primitive neuroectodermal tumor (PNET) of soft tissue
Authors: C. Cano Blanco, G. Calderillo Ruiz, A. Padilla Rosciano, M. Cuellar Hubbe, C. Tenorio, D. Gallardo, M. Aceves Enriquez
Journal: Journal of Clinical Oncology (2005)

9080 Background: PNET are a family of rare and aggressive tumors of presumed neuroectodermal origin, ocurring in children and youhd adults. Treatment in adults is not clearly defined in the literature. The pupose: to evaluate the toxicity and efficacy of the cisplatin/etoposide with or without radiotherapy. Methods: We retrospectively reviewed our therapeutic experience with cipslatin/etoposide. Between 1990 and 2003 we treated 21 patients with soft tissue PNET. Patient characteristics were: gender (male 7, female 14), median age 27 years (range 15–65). Localization: extremities 6, trunk/thorax 12 and head and neck 3 with median tumor size 9 cm. At the diagnosis 12 patients had distant metastases: lung 6, vertebral 2, abdomen 2, pelvis 1 and lymph nodes 1. Treatment: arm (A) 3 patients were treated with surgery folow by chemo-radiotherapy, arm (B) seven with chemo-radiotherapy and arm (C) 11 only chemotherapy. Scheme of chemotherapy: cisplatin 100mg/m2 day 1 and etoposide 100 mg/m2 days 1–3. Results: A total of 90 courses of chemotherapy were administered (median for patient 4). Evaluate for response 16 patients. The arm (B) 7 patients with response (four complete response) with median survival 12 months and arm (C) 3 partial response, 5 progression disease and 1 stable disease with median survival 6 months. In the arm (A) three patients alive and free of disease a 24, 25 and 78 months. The median survival of the group was 10 months. Grade 3/4 toxicities were: neutropenia 8 patients (38%), nauseas-vomiting 4 patients (19%) and fever and neutropenia 2 patients (6%) Conclusions: This cisplatin-etoposide regimen shows good efficacy and tolerable toxicity. The treatment for PNET is needed with multidisciplinary (surgery and chemoradiotherapy). No significant financial relationships to disclose.
Analysis of phase II studies for the year 2002: Design, conclusions and impact factors of oncology vs. non-oncology trials
Authors: L. C. Michaelis, M. J. Ratain
Journal: Journal of Clinical Oncology (2005)

6059 Background: Phase II trials serve as an essential element of drug development. However, analysis of trial design characteristics is limited. We evaluated all abstracts of published phase II trials in 2002. Our aim was to compare trial design, characteristics and conclusions across the spectrum of medical subspecialties. Methods: We screened MEDLINE for abstracts published in 2002 and which included the words “Clinical Trial” and “Phase II.” All abstracts were analyzed and classified by a priori-defined variables including: study type, intervention, subspecialty, journal impact factor, method of control, study conclusions. Results: Our search yielded 703 abstracts of Phase II trials published in 2002. A total of 586/703 (83%) were oncology trials. The remaining 117 represented more than 24 other medical and surgical subspecialties. Just 20 percent (143/703) of the trials included explicit control subjects. Oncology trials were significantly less likely to utilize control subjects (13% vs. 56%, p<0.001) and to conclude that the investigational intervention was safe and efficacious and/or worthy of additional investigation (76% vs. 89%, p<0.01). Approximately 19% of phase II trials were published in journals with impact factors greater than 4.0. Oncology trials were significantly less likely to be published in journals with an impact factor greater than 4.0 (18% vs. 28%, p<0.01). Conclusions: The number of phase II trials published by oncologists far outweighs the number published by other medical specialties. A very small percentage of phase II trials include control subjects with which to judge the safety or efficacy of the tested intervention. However, non-oncology trials are significantly more likely to control for their interventions than non-oncology trials. We conclude that there are significant differences in the phase II trials published in oncology compared to other medical specialties. The impact such differences have on the efficiency of drug development should be investigated. No significant financial relationships to disclose.
Imaging in early breast cancer
Authors: J. R. Hoverman, K. Radebaugh
Journal: Journal of Clinical Oncology (2008)

6594 Backgound: Imaging must 1) uniquely define extent of disease, 2) lead to change in management, 3) that change must improve outcomes based on cost and benefit. This report summarizes the rate of upstaging by imaging for a defined cohort of early breast cancer (EBC) patients. Methods: The first 500 patients with breast cancer in 2005 were identified through the cancer registry. All patients were seen by one community based physician group. The frequency of upstaging by imaging was determined for all patients by chart review. Results: Of 500, 25 had incomplete data, leaving 475. 20, or 4.2% had M1 disease. No patients with T0 or T1N0 were upstaged to M1. Of 163 with T1N1, T2N0–1 or T3N0 (clinical Stage II), 1 was upstaged with imaging alone (0.6%) but had a 20 lb weight loss. Of 63 with T1–3,N2,or T3N1–2 disease (clinical Stage III), 3 (4.8%) were upstaged by imaging alone although 1 had weight loss and fatigue. All other patients were upstaged clinically. If weight loss and fatigue are considered clinical indications for imaging, no patients with clinical Stage II and 2 (3.2%) with clinical Stage III disease were upstaged by imaging alone. Conclusion: Upstaging by imaging alone is a rare event in N0 or T1–2NO-1 disease. For T3N1 or T1–3N2 disease, upstaging by imaging in the absence of symptoms, signs or laboratory abnormalities is infrequent enough to recommend a prospective cost/benefit analysis. The burden of metastatic disease is usually clinically apparent. No significant financial relationships to disclose.
A public hospital experience with young gastric cancer patients.
Authors: Bryan S. Goldner, Jonathan Velasquez, Bruce E. Stabile, Steven L. Chen, Joseph Kim, Matthew Lin, Amy Caton, Byrne Lee
Journal: Journal of Clinical Oncology (2013)

30 Background: Recent literature has reported an increased incidence in the United States of node positive and metastatic disease in young patients with gastric adenocarcinoma. The purpose of this study was to investigate the effect of age (≤40 years) on patients with gastric adenocarcinoma at a large urban public institution. Methods: A total of 520 cases of gastric adenocarcinoma treated between 1995 and 2012 were identified. Information was gathered from the medical record including age at presentation, stage at presentation, pathological type of GC, treatment received, and mortality data. Descriptive statistics were used to analyze the data. Survival was analyzed using the Kaplan-Meier method. Comparisons were made using the log-rank test. Results: The mean age at diagnosis was 56 years. 64 patients (12%) were identified as ≤40 years old. 57 of 64 (89%) of the young age group presented with stage III or IV disease, compared with 75% of patients &gt;40 years of age (p=0.014). For patients ≤40 years old, 38% underwent an operation with curative intent, which was comparable to 39% in patients &gt;40 years old. Of patients who underwent surgery, only 33% (10 of 30) ≤40 years old received an R0 resection compared to 110 of 184 (60%) in those &gt;40 years old (p=0.007). The overall median survival was 5 months with one-year survival of 24% for the young patients and a median of 7.8 months with 39% one-year survival for the older patients (p=0.016). Conclusions: There is a decreased awareness and therefore suspicion of the diagnosis of gastric cancer in young patients (≤40 years of age). For this reason, young patients with gastric adenocarcinoma may present with more advanced disease than older patients. Surgical exploration was often futile, and survival was especially poor in young patients likely due to the more advanced nature of their disease at diagnosis.
CHOP Plus Rituximab (CHOP-R) in Fludarabine (F) Refractory Chronic Lymphocytic Leukemia (CLL) or CLL with Autoimmune Hemolytic Anemia (AIHA) or Richter’s Transformation (RT): First Interim Analysis of a Phase II Trial of the German CLL Study Group (GCLLSG).
Authors: Barbara F. Eichhorst, Raymonde Busch, Ulrich Duehrsen, Holger Schulz, Clemens M. Wendtner, Maria E. Goebeler, Michael Hallek
Journal: Blood (2005)
Identification, categorization, and mapping of indicators used by JACIE-accredited stem cell transplantation programs to assess distribution and coverage of processes.
Authors: Caunday Olivia, Agulles Odette, McGrath Eoin, Empereur Fabienne, Stoltz Jean Francois, Chabannon Christian
Journal: Journal of Clinical Oncology (2012)

255 Background: More than 145 European hematopoietic stem cell transplantation (HSCT) programs received JACIE accreditation since 2000, demonstrating compliance with FACT-JACIE international standards. The association of JACIE with improved patient outcome was recently documented. Conditions in which quality management systems were introduced and actual benefits remain to be fully evaluated. Methods: The study explores one aspect of quality management: introduction and use of indicators. Through a questionnaire sent to JACIE accredited centers, we aimed at identifying indicators (name, domain of application, category, longevity, and general description), understanding how they were set in place, whether or not similar indicators were used by different programs, and whether all of the HSCT processes were monitored. The survey was first sent to 14 French accredited HSCT centers and next to 68 other programs in 11 European countries. Categorization was double-checked against published criteria. Results: The response rate was 40% (32 programs). 293 indicators were collected, including 224 (76%) that were introduced during the preparatory phase of JACIE accreditation. Indicators were associated with the following processes measurement, analysis and improvement (54/293 or 18%); donor collection (49/293 or 16%); processing and storage of cell therapy products (37 /293 or 12.5%), administration of HPC (67/293 or 23%). Mapping reveals an uneven distribution of indicators across the different sub-processes that contribute to this highly-specialized medical procedure. Moreover, we found that only 101/293 indicators (34%) comply with the rules for implementation of a quality indicator, as defined by the FDX 50-171 standard. Conclusions: This suggests that risks to donors/recipients are unevenly monitored, leaving critical medical steps with low levels of monitoring.