tbuckley/cabot-search huggingface dataset:
Adherence to adjuvant endocrine therapy in estrogen receptor-positive breast cancer patients with regular follow-up.
Authors: R. Simon, J. Latreille, C. Matte, P. Desjardins, K. Boudreault, E. Bergeron
Journal: Journal of Clinical Oncology (2010)

e11039 Background: Non-adherence (NAdh) rate to hormonal treatment (HT) has been reported to reach 60%. The goal of this study was to evaluate the level of adherence (Adh) to HT in patients followed in a surgeon's private practice. Methods: From November 2008 to April 2009, all patients with estrogen receptor-positive breast cancer were interviewed at their follow-up visit to the surgeon's office. They were checked for Adh to HT and were asked to detail the reasons for Adh or Nadh. Records were also reviewed for demographics, cancer and treatment characteristics. Qualitative and correlative analyses were carried out. Adh was considered when 100% compliance was reached. Results: Among 398 patients with breast cancer, 161 were eligible: 81% (n = 130) had complete Adh to HT. In patients with Adh, 5 years of HT was completed in 26% (n = 42) and at least 48 months in 36% (n = 58); 52% (n = 88) were ongoing HT at the time of the interview. Median duration on HT was 25 months. Patients reported a unique reason for NAdh (n = 31): forgetting (n = 17); side effects (n = 7); absence of conviction (n = 4); financial problems (n = 1); other acute diseases (n = 1); metastatic disease (n = 1). Patients reported various reasons for Adh: importance of the diagnosis of cancer (100%), fear of recurrence (100%), regular follow-up and supervision by physician and/or nurse (61%), meticulous personality (22%), use of helping device (18%), other medication and/or other medical problems (13%), history of cancer in family and circle (11%), working in the medical or paramedical field (8%), influence of friends and family (5%), inclusion in a research project (3%), and the presence of young children (3%). Multivariate analysis showed that HER2 positivity and postoperative chemotherapy were significantly associated with NAdh (p < 0.05). Conclusions: Adh to HT can be evaluated in a private office practice. Fear of cancer and/or recurrence along with regular follow-up appear to influence Adh to HT. The use of a specific interview to evaluate Adh proved to be a useful tool. Further follow-up and studies should be done to evaluate the relationship between the data and the contribution of regular follow-up by cancer specialist in the Adh to HT. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Genomic Health, Novartis
Panitumumab or cetuximab combined with irinotecan in patients with KRAS wild-type metastatic colorectal cancer previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimens.
Authors: Nobuaki Ikezawa, Satoru Iwasa, Hirokazu Shoji, Yoshitaka Honma, Atsuo Takashima, Natsuko T. Okita, Ken Kato, Yasuhiro Shimada
Journal: Journal of Clinical Oncology (2014)

642 Background: Panitumumab and cetuximab are known to be effective in KRAS wild-type metastatic colorectal cancer (mCRC). However, it is not clear whether panitumumab and irinotecan confers benefit that are comparable to those of cetuximab and irinotecan in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimes. Methods: We analyzed 139 patients who had received panitumumab or cetuximabu combined with irinotecan for KRAS wild-type mCRC previously treated with fluor opyrimidine-, oxaliplatin-, and irinotecan-based regimes.We evaluated and compared efficacy and safety of panitumumab plus irinotecan and cetuximab plus irinotecan. Results: Baseline characteristics were similar for the two groups receving cetuximab pulus irinotecan (n = 97) and panitumumab plus irinotecan (n = 42),respectively.In patients with measurable lesions,the response rate (unconfirmed complete or partial response) were 20% (18/92) in the group receving cetuximab plus irintecan and 34% (14/41) in that receving panitumumab plus irinotecan. Median progression-free survival was 5.7 months in the cetuximab plus irinotecan group versus 4.3 months in the panitumumab plus irinotecan group. Median overall survival was 11.2 months in the cetuximab plus irinotecan group versus 13.6 months in the panitumumab plus irinotecan group. The most common adverse events in the cetuximab plus irinotecan versus panitumumab plus irinotecan groups were all-grade rash acneiform (82% versus 90%), paronychia (61% versus 52%), and grade 3-4 neutropenia (26% versus 19%). Conclusions: Panitumumab or cetuximab plus irinotecan were well tolerated and produced similar response rate and survivals compared to those previous clinical traials.These combinations are cosidered as standard treatment in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based regimes.
Decreased Infections in Recipients of Unrelated Donor (URD Hematopoietic Cell Transplantation (HCT) from Donors with An Activating KIR B Genotype (B/x)
Authors: Marcie Tomblyn, Jo-Anne Young, Michael D Haagenson, John P. Klein, Jan Storek, Stephen Spellman, Sarah Cooley, Daniel J. Weisdorf, Jeffrey S. Miller
Journal: Blood (2008)
The prognostic role of calretinin expression and neutrophil-to-lymphocyte ratio (NLR) in patients with malignant pleural mesothelioma (MPM) undergoing extrapleural pneumonectomy (EPP).
Authors: S. C. Kao, S. Klebe, D. Henderson, G. Reid, M. D. Chatfield, N. Armstrong, T. Yan, J. L. Vardy, S. J. Clarke, N. Van Zandwijk, B. McCaughan
Journal: Journal of Clinical Oncology (2011)

10545 Background: Survival after EPP is variable. Currently there are no validated prognostic factors that can be used to select patients for this procedure. We have investigated the expression of calretinin and D2-40, both associated with tumour differentiation, as well as NLR, an index of systemic inflammatory response as potential preoperative prognostic factors for patients undergoing EPP. Methods: All MPM patients who underwent EPP at participating institutes were included in this retrospective study. Potential prognostic factors such as age, gender, histological subtype, baseline laboratory parameters (white blood cell and platelet count, hemoglobin, and NLR), and immunohistochemical expression of calretinin and D2-40 (scored based on percentage of cells labeled) were evaluated. Overall survival (OS) from the date of surgery was determined by the Kaplan Meier method. The prognostic value of the variables was examined using Cox regression and significant factors (p<0.05) were entered into a multivariate model together to determine their independent effect. Results: A total of 85 patients were included: median age 58 years (range: 22-74); 80% male; 77% epithelial and 23% biphasic MPM. The median OS was 19.7 months (95% CI: 13.8 – 25.6). The following variables were predictive of longer OS: female gender (p=0.02), epithelial histological subtype (p=0.04), low NLR (p<0.01), and high calretinin score (p<0.001). The median OS was 26.7 months vs. 12.6 months for NLR <3 and ≥3 respectively, while it was 35.8 vs. 14.5 vs. 6.9 months for calretinin scores >67%, 34-67% and ≤33% respectively. After multivariate analysis, NLR ≥3 (HR 1.79; 95% CI, 1.04-3.07; p=0.04), and calretinin score ≤33% vs. >67% (HR 4.72; 95% CI, 1.97-11.32; p<0.01) remained independent predictors. Conclusions: Low calretinin expression (poorly differentiated tumours) and high NLR (exaggerated systemic inflammatory response) were independently associated with poor prognosis in MPM patients undergoing EPP. Both calretinin and full blood counts are routinely available and their prognostic value should be validated in a prospective manner.
Construct a computer simulation model to replicate CT operations for decreasing delayed procedure starts.
Authors: Ranganath K. Iyer, Joseph Rodgers Steele, Habib Tannir, Steve Venable
Journal: Journal of Clinical Oncology (2014)

132 Background: Patients scheduled to undergo computed tomography (CT) should be treated expeditiously and not delayed owing to a lack of either CT scanner capacity or available staff. Delayed scanning affects both patients and staff in several ways. First, patients are unhappy that they have to wait. Also, delayed scanning makes patient late for their next appointments or other events, which affects the downstream departments’ capability to operate effectively and efficiently. In addition, radiologists and their staff have to commit additional time and resources to processing patients on time. Finally, variability in the placement of patients reduces the scanner’s operating efficiency. The aim of this initiative is to optimize the appointment template using simulation software to reduce the rate of delayed CT procedures by 25% or more by the end of 2014. Methods: To further understand the CT queuing process, we hired 2 graduate students to create a simulation model using the data collected from the operations study. The simulation study modeled patients’ experience from their arrival to discharge and the steps were: (a) performed elemental analysis for each process; (b) cceated value stream map; (c) created high-level simulation model and “mini model” using operational data. The simulation models were presented to department leaders, who approved them. The models clearly showed that the time patients spent on the CT scanner was the bottleneck. Results: Changes in the CT area that have impacted on-time starts and average wait time include: (a) new fast-track for no interview patients and (b) changes in staffing hours. Progress and improvement include (a.) On-time delays decreased by 18% and (b.) a verage wait decreased by 8 minutes (19%). Conclusions: Discrete event simulation accounts for the probabilities and uncertainties associated with the processes and helps create a visual model of the work area. This adds confidence to decision makers’ ability to make decisions that have high impact. Also, the models can be used to test changes in the processes and study the impact on other processes without making true operational changes that could potentially waste resources and time.
Final results of the international, expanded-access program of everolimus in patients with advanced renal cell carcinoma who progress after prior vascular endothelial growth factor receptor–tyrosine kinase inhibitor (VEGFr-TKI) therapy.
Authors: V. Grünwald, P. I. Karakiewicz, S. E. Bavbek, K. Miller, J. H. Machiels, S. Lee, J. M. G. Larkin, P. Bono, S. Y. Rha, D. E. Castellano, C. U. Blank, J. J. Knox, R. Hawkins, R. R. Yuan, M. Rosamilia, J. L. Booth, I. Bodrogi
Journal: Journal of Clinical Oncology (2011)

4601 Background: The phase III RECORD-1 trial established everolimus as the only agent proven to benefit patients with metastatic renal cell carcinoma (mRCC) after failure of initial VEGFr-TKI therapy. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, more than doubled median progression-free survival compared with placebo, from 1.9 months to 4.9 months. The REACT (RAD001 Expanded Access Clinical Trial in RCC) study was initiated in order to address an unmet medical need and provide everolimus in advance of regulatory approval and commercial availability to patients with mRCC after failure of initial VEGFr-TKI therapy. Methods: REACT was an open-label, international, expanded-access clinical trial (Clinicaltrials.gov: NCT00655252). Eligible patients had measurable or nonmeasurable mRCC of any histology, were intolerant of, or progressed while on, VEGFr-TKI therapy, had a Karnofsky performance score ≥70%, and had adequate bone marrow, hepatic, and renal function. Patients received everolimus 10 mg/day orally, with dose and schedule modifications allowed for toxicity. The primary objective of REACT was to evaluate the long-term safety of everolimus in patients with mRCC, as determined by the overall incidence of grade 3/4 and serious adverse events (AEs). Tumor response to everolimus was also assessed according to RECIST. Results: A total of 1367 patients from 34 countries were enrolled. Safety findings and tumor responses were consistent with those observed in RECORD-1. The most commonly reported grade 3/4 AEs were anemia (13.4%), fatigue (6.7%), and dyspnea (6.4%), and the most frequent serious AEs were dyspnea (5.0%), pneumonia (4.7%), and anemia (4.1%). Median dose intensity was 10.0 mg/day; relative dose intensity ranged from 0.90 to 1.10 in 68.9% of patients. Conclusions: REACT evaluated the safety and tolerability of everolimus in a broader patient population than the controlled trial RECORD-1. Everolimus was well tolerated, with no new safety issues identified and infrequent dose reductions/interruptions in the majority of patients.
Comparison of radical treatment and mortality in patients with nonmetastatic prostate cancer in England and the United States.
Authors: Ashwin Sachdeva, Jan van der Meulen, Paul Cathcart
Journal: Journal of Clinical Oncology (2014)

46 Background: Prostate-cancer mortality in the U.S. is amongst the lowest globally. Given historical differences in management between England and the U.S., this paper aims to determine if risk-adjusted prostate-cancer mortality is inferior amongst men in England compared to the U.S. Methods: Patients diagnosed with non-metastatic prostate-cancer between 2004 and 2008 were identified using English hospital admission records linked to national cancer registry data, and the American Surveillance, Epidemiology and End Results program. Complete data were available for 222,163 patients. Patients were stratified into low-, intermediate-, and high-risk groups according to disease characteristics. Patient demographics from the two countries were compared using the Chi-square test. Competing-risks survival analyses were used to estimate relative six-year prostate-cancer mortality. Results: In comparison to patients in the U.S., English patients were more likely to present at an older age (70 to 79: England 44.2%, USA 29.3%, p&lt;0.001), with higher clinical tumour stage (cT3-4: England 25.1%, USA 8.6%, p&lt;0.001) and higher Gleason score (GS 8-10: England 20.7%, USA 11.2%, p&lt;0.001). They were also less likely to receive radical therapy, with greatest disparity amongst patients with high-risk disease (England 30%, U.S. 83%, p&lt;0.001). After adjusting for age, ethnicity, year of diagnosis, Gleason score, and tumour stage, English patients were more likely to die of prostate cancer (all risk groups: HR 1.9, 95% CI 1.7-2.0, p&lt;0.001). However, this difference was no longer statistically significant on adjustment for radical therapy (all risk groups: HR 1.0, 95% CI 1.0-1.1, p=0.336). Conclusions: After risk adjustment, prostate-cancer mortality is significantly higher in England compared to the U.S. for men with intermediate- and high-risk disease. This difference appears to be explained by decreased use of radical therapy in England.
Evaluation of the necessity of primary tumor resection for synchronous metastatic colorectal cancer.
Authors: Yuji Miyamoto, Yasuo Sakamoto, Satoshi Ida, Masayuki Watanabe, Hideo Baba
Journal: Journal of Clinical Oncology (2012)

592 Background: Recent advances in chemotherapy have improved survival in patients with metastatic colorectal cancer. Resection of primary tumor for patients with metastatic colorectal cancer remains controversial. Primary tumor with obstruction or bleeding may be recommended to resection pior to chemotherapy. In contrast, it should be considered potential complications associated with resection of primary tumor and disadvantage of the delay in chemotherapy. Here, we evaluate the needs of primary tumor resection for colorectal cancer patients with synchronous metastases. Methods: A retrospective analysis of patients with synchronous metastatic colorectal cancer treated at Kumamoto University Hospital between April, 2005 and December, 2009 was performed. We compared the survival of resected patients and non-resected patients. Results: 104 patients were identified. Sixty-four and 40 patients were included in the resected group and the non-resected group respectively. The mean follow-up time was 16.1 months. Median age was 61.9 and 64.3 years respectively. The non-resected group was more likely to have right-sided tumors (resected: 28%, non-resected: 43%). The number of patient with metastatic disease limited to the liver was similar in both group(resected: 48%, non-resected: 50%). In the resected group, 12 patients (18%) developed postoperative complications. In the nonresected group, 5 patients (12.5%) required creation of a diverting colostomy during the course of their treatment due to obstruction, and 2 patients (5%) required emergency surgical treatment for intestinal perforation due to the primary tumor. No significant difference in survival was observed between the groups, (logrank P=0.33). Median survival period was not significantly different (resected: 27.3 months, non-resected: 21.5 months, P=0.43). Conclusions: We concluded that it was not necessary to resect the primary lesion in patients with synchronous metastatic colorectal cancer when obstruction or bleeding was not found in primary lesions.
Circulating cancer cells (CCC) in breast cancer (BC) patients
Authors: K. H. Tkaczuk, D. A. Vanecho, N. Tait, F. Feldman, Z. P. Lum, S. Lesko, P. O.-P. Ts’o
Journal: Journal of Clinical Oncology (2005)

504 Background: Numbers and characterization of CCC may provide information relevant to prognosis and treatment of cancer patients (Pts.). We conducted a blood sampling study in pts. with histologically confirmed BC to assess for presence of CCC. Methods: Approximately 15 ml of venous blood were collected (before systemic therapy and periodically thereafter) and processed with a negative selection procedure using double-gradient centrifugation and magnetic cell sorting to remove RBC and WBC. The cells were stained with anti-pancytokeratin-FITC cocktail and DAPI (DNA stain). Digital images of FITC-positive cells were acquired with a fluorescence microscope for enumeration of CCC. Cells from 21 pts. were also stained simultaneously with labeled Trastuzumab antibody to quantify the HER-2/neu expression relative to a fluorescence standard. Results: 74 pts were accrued and 203 blood samples were drawn; median number of samples drawn per patient was 3 (1–5). Patient characteristics: median age 52 (32–84), race Caucasian -33, African American - 38, Asian-3. Nine pts. were stage I (0-positive for CCC), 16 stage II (6 -positive), 18 stage III (5-postive), 31 stage IV (25-positive). Mean number of CCC per sample was 62, range (1–1283), stage II and III 4, range (1–37), stage IV 76, range (1–1283). Minimum of 5 CCC per sample were needed to assess HER-2/neu receptor expression as compared with strongly HER-2/neu positive control cell line SKBR-3. Eight pts. had sufficient number of CCC to test for HER-2/neu expression. In 5 pts. the CCC and tumor data concurred and were negative, 1 patient was negative by CCC but tumor measured 3+ by IHC and in 2 pts. CCC were HER-/neu positive but tumor was not tested. Conclusions: CCC are related to presence of distant metastasis; but pts. with stage II and III disease may have CCC, the prognostic significance of which is unclear. CCC numbers ranged from 1 to several hundred per draw and fluctuated in the same patient depending on the response to systemic therapy. HER-2/neu expression could be quantified in individual CCC; in most cases CCC and primary tumor data concurred, however some exceptions were noted. Supported in part by NCI SBIR grant to CCC Diagnostics. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CCC Diagnostics LLC CCC Diagnostics LLC CCC Diagnostics
Ferumoxytol enhanced MRI for lymph node staging in prostate cancer.
Authors: Anna Mary Brown, Sandeep Sankineni, Marcelino Bernardo, Dagane Daar, Juanita Weaver, Yolanda McKinney, Anna Couvillon, James L. Gulley, Peter A. Pinto, William L. Dahut, Ravi Amrit Madan, Peter L. Choyke, Baris Turkbey
Journal: Journal of Clinical Oncology (2015)

208 Background: Conventional imaging methods of lymph node staging in prostate cancer are limited. The goal of this study is to determine the utility of ferumoxytol enhanced MRI in lymph node (LN) staging. Methods: This ongoing IRB-approved clinical trial enrolls prostate cancer patients at high risk for LN metastases. Patients first undergo baseline T2 and T2* weighted MRI scans followed by 7.5mg/Kg ferumoxytol injection. Repeat scans are acquired at 24 hr and 48 hr post-injection. The criterion for positive LNs was hyperintense signal indicating failure to take up ferumoxytol. Validation was determined on clinical grounds or by histopathology when available. Results: To date, 11 patients have completed the study. One patient was examined pre-operatively while the other 10 had suspected therapy failure. Median age and PSA were 65 yrs (36-75) and 5.6ng/dL (0.3-201). Of 16 LNs with median size 1.6 x 1.1cm, 10 were true positives, one was false positive and one was false negative with 4 nodes pending validation. The LN status was correctly identified in 8 of 11 patients [Table]. Conclusions: Ferumoxytol enhanced MRI shows promise in detecting malignant LNs with diameter &gt;6mm in prostate cancer paients. This method is performed in a conventional MRI unit with off-label use of an FDA-approved agent and thus could be widely available. However, further validation is necessary before routine use. Clinical trial information: NCT02141490. [Table: see text]
A phase I study with a daily regimen of the oral mTOR inhibitor RAD001 (Everolimus) plus sorafenib for patients with metastatic renal cell cancer (MRCC)
Authors: S. Giessinger, R. J. Amato, J. Jac, S. Saxena, J. P. Willis, S. B. Chiang
Journal: Journal of Clinical Oncology (2008)

14603 Background: Emergence of targeted therapy for MRCC has been a turning point in improving outcomes. Evaluation of a tyrosine kinase inhibitor (TKI) plus an mTOR inhibitor to increase the magnitude and duration of anti-angiogenic effect, and potentially to overcome the development of resistance is being evaluated. Phase I study to determine the maximum tolerated dose, data on response rate, progression free survival (PFS) and overall survival (OS) was assessed. Methods: Predominantly clear cell RCC, progressive measurable metastatic disease, adequate organ/marrow function, no more than 3 prior therapies, and no active CNS involvement. Everolimus and sorafenib are administered orally, daily without interruption. A treatment cycle is 28 days. Dose modifications were performed per the National Cancer Institute, toxicity criteria version 3.0. Dose levels are: shown in the Table. Patients are evaluated every 4 weeks and after every 2 cycles (8 weeks) using RECIST. CT PET imaging is performed at baseline and first restaging to determine changes in the metabolic activity compared to the traditional response criteria. Results: 13 Patients were enrolled to date, 7 pts were enrolled on dose level 0 (1 pt was replaced due to only receiving Everolimus for 2 days). Adverse events included; Grades 1/2: hand-foot syndrome (69%), rash (62%), diarrhea (54%), and stomatitis (38%). Grade 3/4 adverse events included: hand-foot syndrome (17%), pneumonitis (8%), pleural effusion (8%), and thrombocytopenia (8%). Partial responses were seen in 7 (58%), stable disease ≥ 3 months, 4 (30%), progressive disease, 1 (8%). PFS and OS are too early. Conclusions: Everolimus combined with sorafenib is well tolerated with reversible toxicities. We are actively enrolling for dose level +2. The combination demonstrates encouraging anti- tumor activity as indicated by tumor responses. Safety data and anti-tumor activity will be presented in addition to correlation with radiographic studies and metabolic imaging. Dose Levels Everolimus mg Sorafenib mg 0 2.5 400 +1 5 400 +2 10 400 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis