tbuckley/cabot-search huggingface dataset:
Interim follow up results from a phase II study of neoadjuvant chemoembolization of resectable colorectal liver metastases (CRLM) with transcatheter hepatic therapy with irinotecan-eluting beads.
Authors: Robert Peter Jones, Hassan Zakria Malik, Stephen W Fenwick, Monica Terlizzo, Elizabeth O'Grady, Stefan Stremitzer, Thomas Gruenberger, Graeme John Poston
Journal: Journal of Clinical Oncology (2013)

519 Background: 65% of patients undergoing liver resection for CRLM experience disease recurrence within 3 years. Perioperative chemotherapy improves 3-year progression free survival, and good pathologic response is associated with improved overall survival. However, systemic neoadjuvant chemotherapy increases operative morbidity. DEBIRI gives sustained delivery of drug directly to tumor, maximising response and reducing systemic exposure. This study examined the feasibility, safety and long-term outcome of patients treated with neoadjuvant DEBIRI before resection. Methods: Patients with resectable CRLM received single targeted DEBIRI (up to 200mg) 1 month pre-hepatectomy. Primary end-point: tumor resectability, secondary end-points: safety, pathologic response, disease-free (DFS) and overall survival (OS). Results: DEBIRI performed in 40 patients. Post-TACE complications: 1 acute pancreatitis (3%); 4 post-embolization syndromes (10%). 38 patients underwent hepatectomy (2 peritoneal disease, resectability rate 95%). 30-day operative mortality 5% (n=2), neither death TACE related (1 intraoperative pneumomediastinum, 1 aspiration pneumonia). Both operative deaths excluded from follow up analysis. 63 lesions (median 2 per patient) targeted with DEBIRI. Histology: no residual disease 17%; 1-49% residual disease 59%; &gt;50% residual disease 22%; no response 2%. Median follow up 293 days. Fourteen patients (36%) had disease recurrence, median DFS 387 days (95% CI 276-498). Eight (57%) had hepatic recurrence, 2 (14%) had pulmonary recurrence and 4 (29%) had both pulmonary and hepatic recurrence. One patient died of hepatic and pulmonary recurrence after 565 days. Conclusions: Resection after neoadjuvant DEBIRI for CRLM demonstrated a good safety profile in this study population. Single DEBIRI treatment resulted in impressive pathologic response, with patterns of recurrence comparable to reported series of resection alone. Further trials assessing combination DEBIRI and systemic chemotherapy are necessary. Clinical trial information: NCT00844233.
Women's understanding of personal breast cancer risk: Does ethnicity matter?
Authors: Jonathan D. Herman, Sarah M. Herman
Journal: Journal of Clinical Oncology (2013)

4 Background: A woman’s understanding of her breast cancer risk is an important precursor for care. A valid estimate allows for greater opportunity to consider early detection modalities and chemopreventive medications. The USPSTF recently encouraged women who have an increased risk of developing a first breast cancer and a low risk of side effects to take tamoxifen or raloxifen. The objective of this study is to compare patients' perceived breast cancer risk with their calculated risk and then parse those findings by ethnicity. Methods: Anonymous, IRB approved, pre-piloted questionnaires were filled out by women at 21 mammography centers on Long Island. The survey included questions about patient demographics, patient’s estimates of their own breast cancer risk and personal risk factors. Results: 9,873 respondents qualified for inclusion in our analysis. Women were asked to quantify their breast cancer risk by age 90. Overall, 707 (9.4%) were in line with their risks, 3,359 (44.7%) underestimated risk and 3,454 (45.9%) overestimated their risk. When parsed by ethnicity, of the 781 African Americans, 8.7% were in line, 57.6% underestimated risk, and 33.7% overestimated risk. Of the 245 Asians, 10.2% were in line, 58.8% underestimated risk, and 31% overestimated risk. Of the 427 Hispanics, 8.9% were in line, 50.4% underestimated risk, and 40.8% overestimated risk. Of the 6850 Caucasians, only 10.2% were in line, 38.6% underestimated risk, and 51.3% overestimated risk. Conclusions: Most women lack accurate knowledge of their own breast cancer risk – 90.6% overall. When parsed by ethnicity, while there was a statistical difference between groups, the difference was not important because overall understanding was very low. Caucasian women tended to overestimate their risk compared with other ethnic groups, possibly resulting in unnecessary anxiety. African American and Hispanics tended to underestimate risk compared with Caucasians, possibly resulting in underutilization of available resources. Patients must have a better understanding of their personal risk. Study findings should help refocus educational efforts because increased knowledge of breast cancer risk will enable providers to tailor an individual’s medical treatment plan.
Pretreatment plasma concentrations of YKL-40 and IL-6 in patients with pancreatic cancer: Potential diagnostic and prognostic biomarkers.
Authors: Nicolai Aagaard Schultz, Ib Jarle Christensen, Jens Werner, Nathalia Giese, Benny Vittrup Jensen, Ole Larsen, Jon Kroll Bjerregaard, Per Pfeiffer, Dan Calatayud, Svend Erik Nielsen, Mette Yilmaz, Niels Henrik Hollander, Morten Wøjdemann, Stig E. Bojesen, Kaspar Nielsen, Julia S. Johansen
Journal: Journal of Clinical Oncology (2013)

164 Background: To test the hypothesis that high pretreatment plasma YKL-40 and IL-6 associate with pancreatic cancer (PC) and short overall survival (OS). Methods: 556 patients with PC from Denmark (N=445) and Germany (N=111) were included in the present prospective biomarker study. 152 (27%) patients were operated and treated postoperative with adjuvant gemcitabine. 404 (73%) had locally advanced or metastatic PC and received palliative chemotherapy (primarily gemcitabine). Pretreatment plasma YKL-40 and IL-6 were determined by ELISA with known reference intervals in healthy subjects. Results: The OR for prediction of PC in the whole study population was significant for all 3 biomarkers with CA 19-9 having the highest AUC (YKL-40: OR=4.50, 95% CI 3.99-5.08, p&lt;0.0001, AUC=0.87; IL-6: OR=3.68, 3.08-4.44, p&lt;0.0001, AUC=0.87; CA 19-9: OR=2.28, 1.97-2.68, p&lt;0.0001, AUC=0.93). YKL-40, IL-6 and CA-19-9 increased with more advanced stage (YKL-40 median (IQR): Stage IA-IIA 100 (68-157), IIB-III 101 (59-179), IV 166 (89-296) μg/L, p&lt;0.0001; IL-6: Stage IA-IIA 4.2 (1.9-8.9), IIB-III 4.0 (2.1-8.2), IV 7.4 (3.6-18) ng/L, p&lt;0.0001); CA-19-9: Stage IA-IIA 58 (10-622), IIB-III 209 (54-856), IV 1041 (146-9178) ng/L, p&lt;0.0001). Univariate Cox analysis in resected patients showed that only pretreatment IL-6 and CA 19-9 (dichotomized according to normal values) were associated with short OS (YKL-40: HR=1.38, 0.87-2.18, p=0.17; IL: HR=2.23, 1.41-3.52, p=0.0006; CA 19-9: HR=2.80, 1.54-5.09, p=0.0007). In non-resectable patients all 3 biomarkers were associated with short OS (YKL-40: HR=1.54, 1.23-1.93, p=0.0001; IL: HR=1.63, 1.29-2.06, p&lt;0.0001; CA 19-9: HR=1.48, 1.02-2.15, p=0.039). Multivariate Cox analysis in non-resectable patients (YKL-40, IL-6, CA 19-9 (log transformed base 2), age, sex, and stage) demonstrated that YKL-40 (HR=1.12, 1.02-1.23, p=0.021), IL-6 (HR=1.20, 1.09-1.31, p=0.0001) and CA 19-9 (HR=1.10, 1.07-1.14, p&lt;0.0001) were independent biomarkers for short OS. This was not found in resected patients. Conclusions: Pretreatment plasma concentrations of YKL-40 and IL-6 may be new diagnostic and prognostic biomarkers in patients with PC.
The “Big 6 Spotlight”: Baseline assessment and implementation of a process to systematically collect critical oncology data elements for quality improvement and research.
Authors: Edward C. Li, Steven L. D’Amato, Thomas R. Barr, Tracey Weisberg
Journal: Journal of Clinical Oncology (2012)

312 Background: An Institute of Medicine (IOM) report recommends using electronic health record data for quality improvement and research. To do so, a critical density of data elements must exist. Oncology Metrics, a division of Altos Solutions, Inc. identified 6 data elements (“The Big 6”) of high priority for obtaining data density: 1) staging; 2) intent of therapy; 3) adverse event grade; 4) disease status; 5) patient status; 6) line of therapy. Process improvement measures are being implemented to improve the prospective, systematic reporting of the Big 6 by practices using OncoEMR. An analysis of data element completion frequency is necessary to provide feedback to clinicians in support of a process improvement strategy. Practices also require benchmark information to compare their performance with expectations and the aggregate. Methods: Altos developed the Big 6 Spotlight as a toolbar selection in OncoEMR for physicians to monitor and enter patient Big 6 data elements concurrently with the provision of patient care. Baseline data for 7/2012 was collected for each physician in the practice before they were educated and trained on the data entry program. We report baseline and post implementation information about the density of the Big 6 at one private practice utilizing OncoEMR. Data are also compared to historical and national benchmark data. Results: The percentage of patients/events with staging, intent of therapy, adverse event grade, disease status, patient status, and line of therapy completed was calculated by dividing the number of fields complete by the total number of patients/events. These were: 68%, 6%, 0.3%, 4%, 61%, and 22%, respectively. Post implementation data are not available at the time of this writing. Conclusions: Big 6 data density will be assessed post-implementation of the Big 6 Spotlight initiative to monitor improvement. Data uniformity and consistency will be also be evaluated. Ensuring that this dataset is of high internal validity allows for the conduct of quality improvement and research studies, moving us closer towards achieving a rapid-learning system as described in the IOM report.
PARP inhibition after preoperative chemotherapy in patients with triple-negative breast cancer (TNBC) or known BRCA1/2 mutations: Hoosier Oncology Group BRE09-146.
Authors: S. R. Malireddy, S. M. Perkins, S. S. Badve, G. W. Sledge, K. Miller
Journal: Journal of Clinical Oncology (2011)

TPS130 Background: TNBC patients who do not achieve pathologic complete response (pCR) have an extremely high risk of disease recurrence. Based on recently reported I-SPY trial, TNBC patients who had residual disease category II or III had 2-year disease free survival (DFS) of only ~40% (J Clin Oncol 2009;27:18s). Currently, no standard systemic therapy exists for this high-risk group who represent a real opportunity to explore the potential impact of novel therapies. Recent laboratory and early clinical studies (Nature 2005;434:913, NEJM 2011;10:1056) identified a unique sensitivity to DNA-damaging chemotherapy and PARP inhibition. We initiated a randomized phase II trial of DNA-damaging chemotherapy (cisplatin) or PARP-inhibition + cisplatin in TNBC patients with residual invasive disease after standard anthracycline and/or taxane containing neoadjuvant chemotherapy. Methods: To ensure a high-risk population, patients must have residual disease category 0-2 based on the Miller-Payne classification system, residual cancer burden classification II or III, residual lymph node involvement, or at least 2 cm of residual invasive disease in the breast. After completion of standard radiation therapy, patients will be randomized 1:1 to cisplatin (75 mg/M2 IV Day 1 every 3 weeks x 4 cycles) alone or in combination with PARP inhibition (PF-01367338 - 24 mg IV D1, 2, 3 of each 3 week cycle with a single dose escalation to 30 mg in the absence of significant toxicity in cycle 1 followed by maintenance PARP inhibition weekly x 24 weeks). The primary objective is 2-year DFS. To detect an improvement in 2-year DFS from 40% with cisplatin alone to 63.2% in the cisplatin + PF‐01367338 arm (corresponding to HR=0.5), with 80% power using a one-side log-rank test with 0.10 level of significance, 102 patients are required in the primary analysis. Secondary objectives include safety, 1-year DFS, overall survival, and biomarkers of tumor recurrence, resistance to chemotherapy and/or PARP inhibition. Two dose escalation safety cohorts (N=13) were completed without dose limiting toxicity; the randomized portion began enrolment in 11/2010 and enrolled 6 patients as of 01/2011.
Long-lived melanoma-antigen specific memory T cells in patients with metastatic melanoma vaccinated with melanoma-antigen loaded dendritic cells
Authors: J. W. Fay, H. Ueno, J. Banchereau, A. K. Palucka
Journal: Journal of Clinical Oncology (2008)

20002 Background: Clinical trials have shown safety of cancer antigen-loaded dendritic cells (DCs) as well as clinical and immune responses. We demonstrated antigen-pulsed DCs administered to patients with metastatic melanoma were immunogenic and induced durable objective clinical responses and prolonged survival. Responses and prolonged survival were seen even in patients whose disease progressed after chemotherapy. We report a preliminary analysis of long term immunological outcomes in a cohort of vaccinated patients. Methods: Between March 1999 and February 2005 sixty four patients with metastatic melanoma were treated with DC vaccines in the course of four phase I/IIa clinical trials. DCs were generated either from CD34+ hematopoietic progenitors or from blood monocytes. Forty four (44) HLA-A*0201+ patients received vaccines pulsed with melanoma antigen derived peptides (MART-1, MAGE-3, TYR and gp100). Twenty (20) patients received DCs loaded with killed allogeneic tumors. KLH was used as helper antigen and, in HLA-A*0201+ patients, Flu-M1 peptide was used as control antigen. Patients received up to eight vaccinations with antigen-loaded DCs over a maximum of 7 months. Results: DC vaccinations were safe and tolerable. Nine of 64 patients (14%) are alive (range 39+-105+months) as of January 2008. Median survival was 17 (95% CI 12–26) months. Long-term immunological analysis in this cohort is ongoing. Preliminary studies demonstrated the induction of long-lived melanoma-antigen specific CD8+T cells in a patient who experienced a complete regression of in-transit melanoma by RECIST criteria. In this patient serial DC vaccinations expanded circulating MART-1-specific CD8+ T cells. These cells could be detected in the blood after the 4th and 8th DC vaccination and have persisted over 2.5 years. These T cells had predominantly effector memory phenotype. Conclusions: DC vaccines resulted in clinical benefit and elicited durable objective responses in a fraction of patients with metastatic melanoma. DC vaccines expanded melanoma-antigen specific memory T cells that appear to be long lasting. No significant financial relationships to disclose.
Heterogeneity of treatment effects (HTE) in stage IV prostate cancer (S4PC).
Authors: Nirupama Devi Mitikiri, Emily S Reese, Arif Hussain, Ebere Onukwugha, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2012)

e15108 Background: HTE occurs when patient factors modify a treatment’s effect on health outcomes so patients in the same study have different responses to a specific treatment. Variation in outcomes is caused by interactions between the factors causing HTE and the treatment. HTE may explain some of the heterogeneity in S4PC prognosis. The HTE literature is evolving; hence some factors causing HTE in S4PC are not yet documented. Methods: A systematic literature review (1946-2011) of published trials and observational studies identified evidence of statistically significant factors influencing HTE in S4PC. Inclusion criteria required that articles examine the impact of HTE factors on survival (OS, DSS, PFS) or health-related quality-of-life measures among S4PC patients. Factors that influenced outcomes but were not specifically evaluated in the context of HTE were excluded. Results: Of 398 articles that included key words, 33 met inclusion/exclusion criteria. Treatments included chemotherapy, radiation, hormonal therapy and bone-modifying agents. Both biologic and non-biologic factors (Table) were found to be associated with HTE in S4PC. Evidence was mixed regarding whether HTE in S4PC is influenced by race or by confounding factors correlated with race or both. As no articles examined prognostic factors such as bcl2, PTEN, p53, Pgp and EGFR status in the context of a specific treatment, such factors were excluded. Conclusions: Current evidence reveals diverse factors influencing HTE in S4PC.Ultimately, such knowledge can help oncologists prescribe more personalized medicine, help patients make more informed treatment choices, and aid policy making and treatment coverage decisions. [Table: see text]
CAPIRI (capecitabine, irinotecan) + bevacizumab vs FOLFIRI (folinic acid, 5 fluorouracil, irinotecan) + bevacizumab for the treatment of patients with metastatic colorectal cancer (mCRC): Interim analysis for safety of a randomized phase III trial
Authors: N. Ziras, A. Polyzos, S. Kakolyris, N. Xenidis, N. Kentepozidis, A. Athanasiadis, I. Stergiou, N. Androulakis, L. Vamvakas, J. Souglakos
Journal: Journal of Clinical Oncology (2008)

15008 Background: CAPIRI has been reported to be associated with significant toxicity. Therefore, an unplanned interim analysis for safety of a randomized trial evaluating CAPIRI + Bevacizumab vs FOLFIRI + Bevacizumab regimens for the treatment of mCRC was performed. Methods: Assuming time to tumor progression (TTP) of 7.5 months for Arm B and 5.5 months for Arm B, 280 patients should be enrolled in the study (two-tailed log-rank test; a=0.05, b=0.8).Patients were randomized to receive either (Arm A) CPT-11 (250 mg/m2, d1) and Capecitabine (2,000 mg/m2, d1–14) every 3 weeks (Arm A) or CPT-11 (180 mg/m2, d1), LV (200 mg/m2, d1+2) and 5-FU (400 mg/m2/d bolus and 600 mg/m2/d, 22h infusion, d1+2) every 2 weeks (Arm B). Results: Among the 156 enrolled patients (Arm A = 74; Arm B = 82), were evaluable for toxicity (administered cycles: 1061). Treatment delays were observed in 4% and 2% Arm A and B patients, respectively (p=0.09). Dose reduction was required in 9.5% and 4.5% Arm A and B patients, respectively (p=0.002). Treatment discontinuation due to treatment related toxicity occurred in 13% and 4.5% Arm A and B patients, respectively. Sixty days mortality rate was low in both arms (Arm A: 1.5%, Arm B: 1.2%). There was no difference between the two regimens in terms of objective response rate, TTP and OS (n = 142 patients). Conclusions: These preliminary results show that CAPIRI + Bevacizumab regimen could safely administered in patients with mCRC. No significant financial relationships to disclose.
Value of CA 15-3 detection in cerebrospinal fluid (CSF) of breast cancer leptomeningeal metastases.
Authors: S. Salingue, M. Girot, I. Rodrigues, S. Taillibert, N. Kotecki, F. Zairi, M. Baranzelli, M. Faivre-Pierret, P. Devos, J. Bonneterre, F. Dubois, E. Le Rhun
Journal: Journal of Clinical Oncology (2011)

2075 Background: An increased incidence of leptomeningeal metastases (LM) is reported in breast cancer (BC), which is the predominant etiology of LM in solid tumors Our aim was to assess the significance of intra-CSF CA 15-3 measure in the early diagnosis of BC LM. Methods: Serum and CSF levels of CA 15-3 and albumine were evaluated in 4 groups of 20 patients recruited from April 2008 to January 2011: group A (new diagnosis of BC LM), group B (new diagnosis of various other solid tumors LM), group C (progression of intraparenchymal brain metastasis of BC) and group D (controls without any cancer). CA 15-3 was assessed by automatic immune-enzymatic technology (Kryptor, BRAHMS Biomarkers). Non parametric analysis of variance with Bonferroni correction was used for comparisons of means. Results: In group A, median age was 51,5 years (30-70). LM and intraparenchymal metastases were observed at the MRI in 80% and 75% of patients respectively. CSF cytology was positive in 85% of cases. Median proteinorachia was 1,03 g/l (0,22-16,12). Median CSF/serum albumine ratio were 0,02 (0,006-0,62) in group A; 0,01 (0,004-0,05) in group B; 0,01 (0,004–0,05) in group C; 0,006 (0,002-0,04) in group D. Median rates of inra-CSF CA 15-3 were 8,65 U/ml (0,1-250,9) in group A; 0,55 U/ml (<0,3-213,5) in group B; 0,55 U/ml (<0,3-18,5) in group C; 0,30 U/ml (<0,3-0,3) in group D. Median rates of CA 15-3 in serum were 51,4 U/ml (11,9-2819) in group A; 21,1 U/ml (7,5-296,4) in group B; 30,4 U/ml (11,9-4999) in group C; 40,2 U/ml (6,2-23,8) in group D. Median CSF/serum CA 15-3 ratio were 0,18 (0,004-4,39) in group A; 0,03 (0-3,79) in group B; 0,015 (0,002-0,53) in group C; 0,02 (0,007-0,19) in group D. In group A, intra-CSF and serum 15-3 rates were statistically significantly different from the 3 other groups (p<0,0001). Conclusions: Intra-CSF CA 15-3 assessment may be helpful for early diagnosis of BC LM. The reproducibility of this tool will be validated. Futures studies will be planned to determine a threshold rate for BC LM diagnosis.
Reliability of the CT-SCAN percutaneous biopsy for small renal masses.
Authors: Alexandre Ingels, Eric Barret, Francois Audenet, Luca Lunelli, Guilherme Prada Costa, Francois Rozet, Marc Galiano, Rafael Sanchez-Salas, Stephane Lenoir, Pierre Validire, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2014)

514 Background: The aim of this study was to assess the veracity of the outcomes from renal biopsy performed under CT-scan control for patients harboring cT1a stage tumors. Methods: In a retrospective study, we analyzed the outcomes of renal biopsies performed under CT-scan control for patients harboring tumors under 4 cm. Pathology has been compared between biopsy sample and nephrectomy specimen. Every patient included had a small renal mass (cT1a) and had to undergo a CT-scan guided renal biopsy before nephron sparing or enlarged nephrectomy (that had to be done within 6 months after the biopsy). Results: From January 2007 to December 2012, we performed 79 CT-scan guided renal biopsies. Among these patients, biopsy lead to the diagnosis of the renal lesion for 70 cases. For 9 cases, biopsy was not contributive. Following the biopsy, 19 patients underwent a nephron sparing surgery and 10 a radical nephrectomy. Comparison of the pathological outcomes between biopsy and surgical specimen showed an agreement for the diagnosis of carcinoma in 28 cases (97%): one case of chromophobe carcinoma on biopsy sample analyze happened to be an oncocytoma on the surgical specimen. Sensitivity was 100% and Specificity 67%. Conclusions: Renal biopsy under CT-scan control yield to a trustful diagnosis of small renal mass in most of the cases. It seems relevant to systematically offer this strategy to the patients in order to adapt their following treatment.
The Association of a Single Nucleotide Polymorphism in the Chemokine CXCL10 Gene with Transplant Outcomes After HLA-Matched Unrelated Bone Marrow Transplantation for Low Risk Hematologic Malignancies
Authors: Katsuya Nakata, Luis J. Espinoza, Makoto Onizuka, Takahiro Fukuda, Takakazu Kawase, Eriko Morishita, Yoshihisa Kodera, Yasuo Morishima, Shigeki Ohtake, Shinji Nakao, Akiyoshi Takami
Journal: Blood (2011)