tbuckley/cabot-search huggingface dataset:
Patient navigation for breast cancer patients with disabilities.
Authors: Mary Anne Fenton
Journal: Journal of Clinical Oncology (2013)

130 Background: Patient navigator programs (PNP) aid in evaluation and treatment of cancer in underserved populations. Along a patient’s journey obstacles to medical care can include cultural, financial, language, physical and transportation barriers, fear and anxiety, comprehension and retention of critical information and coordination of visits. PNP research has focused on addressing ethnic and racial barriers, with scant attention paid to the impact of PNP in the disabled. The Americans with Disabilities Amendments Act of 2008 defines as a “physical or mental impairment that substantially impairs one or more of major life activities." Methods: A retrospective analysis was performed of patients with stage I-III breast cancer under age 70 with disabilities enrolled in the PNP at Rhode Island Hospital or the Miriam Hospital (RIH/MH) from 2006-2012. Charts were reviewed and assessed for quality measures as defined by the National Comprehensive Cancer Center (NCCN) guidelines and American Society of Medical Oncology Quality Practice Initiative (QOPI) benchmarks, for demographics, stage at diagnosis, treatment recommended and received, and patient outcomes. Results: 44 patients were identified. All patients were recommended treatment in accordance with NCCN guidelines. Compliance with radiation and endocrine therapy guidelines was excellent. In the smaller cohort of patients for whom adjuvant chemotherapy was indicated, there was a higher rate of nonconcordance (25%) compared to 13% in the NCCN database. All nonconcordance was attributed to patient refusal (6) or delay due to comorbid conditions (3). Conclusions: Our analysis suggests PNP may enhance compliance with recommended treatment and thus quality care in breast cancer patients with disabilities. Integration of PNP in cancer care serves as a valuable adjunct in removing obstacles to cancer care for the disabled. [Table: see text]
Molecular Mechanisms of Parthenolide-Mediated Pro-Apoptotic Activity in Acute Myeloid Leukemia Cells
Authors: Mohammad Minhajuddin, Shanshan Pei, John M Ashton, Kevin Callahan, Eleni Lagadinou, Marlene Balys, Cheryl Corbett, Sarah Neering, Randall M Rossi, Craig T. Jordan
Journal: Blood (2011)
Clinical significance of serum vascular cell adhesion molecule-1(VCAM-1) in colorectal cancer.
Authors: Rumeysa Ciftci, Nuri Faruk Aykan, Ece Aksit, Ceren Tilgen Yasasever, Sezai Vatansever, Vildan Yasasever
Journal: Journal of Clinical Oncology (2015)

550 Background: Vascular cell adhesion molecule-1 (VCAM-1) is a transmembrane glycoprotein, which is expressed on endothelium and contributes in leukocyte adhesion and extravasation during inflammation. It has been demonstrated that VCAM-1 is over-expressed on colorectal cancer (CRC) cells and plays role in metastasis development and angiogenesis. We aimed to compare serum VCAM-1 levels of CRC patients with heathy controls and evaluate its relationship with clinicopathologic parameters, treatment response and overall survival (OS). Methods: The study enrolled 111 patients with histopathologically confirmed CRC followed up between February 2010-September 2013 in Institute of Oncology, Istanbul University and 30 sex- and age-matched healthy controls. Pre-treatment serum VCAM-1 levels were determined by the solid-phase sandwich ELISA method. Results: The cancer localisation was rectum in 40% and colon in 60% of patients. Metastatic disease was present in 51.4%. Forty percent of 40 metastatic patients who received palliative chemotherapy (CT) was CT-responsive (partial or complete response). The median serum VCAM-1 level was significantly higher in CRC patients than controls (p&lt;0.001). In addition, serum VCAM-1 level was significantly higher in diabetic CRC patients than those without diabetes (p=0.03). There was no significant relationship between other clinicopathologic parameters, stage, carcinoembrionic antigen (CEA), CA19.9 and VCAM-1. The median follow-up period was 12 (±8.2) months. Progression was observed in 16.2 % of patients and 18 % of patients had died at the time of analysis. The presence of metastasis (p&lt;0.001) and elevated CEA level (p&lt;0.001) were factors affecting OS significantly. Serum VCAM-1 did not have a significant impact on OS in both univariate (p=0.55) and multivariate analysis (p=0.23). Conclusions: Serum VCAM-1 level is significantly higher in patients with CRC than controls. However, it has no prognostic or predictive role for CT response. Studies randomising CRC patients in more homogenous treatment arms to evaluate the effect of systemic treatment on serum VCAM-1 with longer follow-up period are needed.
Long-term results of the Toronto magnetic resonance imaging (MRI) breast surveillance study of women with <i>BRCA1</i> or <i>BRCA2</i> mutations.
Authors: K. Passaperuma, D. B. Plewes, P. Causer, K. A. Hill, S. J. Messner, J. Wong, R. A. Jong, F. Wright, M. Yaffe, E. Ramsay, S. Balasingham, L. Verity, A. Eisen, B. Curpen, R. Shumak, S. Narod, E. Warner
Journal: Journal of Clinical Oncology (2011)

542 Background: Although the addition of MRI to mammography for breast cancer screening in women with BRCA mutations has been shown to significantly increase sensitivity, some groups have reported high interval cancer and node-positive rates for BRCA1 mutation carriers, and the impact on survival is unknown. We report screening performance, cancer stage, distant recurrence rate, and breast cancer-specific mortality for women with BRCA mutations enrolled in our MRI screening program. Methods: From 1997 to 2009, 496 women ages 25 to 65 (median 44) with a BRCA1(54%) or BRCA2 (46%) mutation, 380 with no previous cancer, were enrolled in a prospective screening trial that included annual breast MRI and mammography. Women underwent a total of 1847 screening rounds (median 3, range 1-9). Results: 57 cancers were identified (53 detected at screening, 1 interval, and 3 incidental at prophylactic mastectomy), of which 37 (65%) were invasive. Sensitivity of MRI vs. mammography was 86% vs. 19% overall (p<0.0001), 74% vs. 35% from 1997 to 2002 (p=0.02), and 94% vs. 9% from 2003 to 2009 (p<0.0001). The relative sensitivities of MRI and mammography did not differ by mutation, age, or invasive vs. noninvasive disease. Overall specificity of MRI vs. mammography was 90% vs. 97%. Of the 37 invasive cancers, 36 were ≤ 2 cm and 33 were node-negative. 97% of incident cancers were stage 0 or 1. Compared to BRCA2 mutation carriers, cancers in BRCA1 carriers were significantly more likely to be ER-negative (p=0.01) and treated with chemotherapy (p=0.04), and trended towards being larger, higher grade and more likely to be invasive. At a mean follow-up of 68 months from cancer diagnosis, only 1 of 28 previously unaffected women with invasive cancer had died of breast cancer, her tumor detected on her first screen at age 48, with no other distant recurrences (annual breast cancer mortality rate=0.6%). Conclusions: Despite a relatively short median follow-up of 5.5 years, given the early relapse pattern of BRCA-related cancers, these results are very encouraging. MRI surveillance appears to be a viable alternative to prophylactic mastectomy for women with BRCA1 or BRCA2 mutations.
Six versus eight cycles of biweekly CHOP-14 with or without R in elderly patients (pts) with aggressive CD20<sup>+</sup> B-cell lymphomas: Seven-year FU of the RICOVER-60 trial of the DSHNHL.
Authors: M. Pfreundschuh, M. Ziepert, S. Zeynalova, E. Lengfelder, H. Steinhauer, M. R. Clemens, C. Nickenig, A. D. Ho, L. H. Truemper, M. Hoffmann, R. H. Mertelsmann, B. Metzner, H. Mergenthaler, V. Poeschel, N. Schmitz, M. Loeffler
Journal: Journal of Clinical Oncology (2011)

8029 Background: Interval reduction from 3 (CHOP-21) to 2 wks (CHOP-14) and the addition of R to CHOP-21 (R-CHOP-21) improved outcome in elderly pts with DLBCL to a similar extent compared to CHOP-21. Methods: In the RICOVER-60 trial, elderly pts.(61-80 yrs) were randomized to receive 6 or 8 cy CHOP-14 with or without 8 cy R. RX was planned to sites of initial bulk and/or extranodal inv. The primary endpoint was EFS, secondary endpoints were PFS and OS. Results:Between 07/2000 and 06/2005, 1,222 pts with CD20+ DLBCL were recruited and are evaluable (med age 68 yrs; IPI=1: 30%, IPI=2: 28%, IPI=3: 26%, IPI=4,5: 16%). There was no difference between the 4 arms with respect to long-term tox and 2nd neoplasms. As by intention to treat, the 7-yr EFS rate was 33% after 6xCHOP-14 (n=307), 40% after 8xCHOP-14 (n=305), 50% after 6xR-CHOP-14 (n=306), and 52% after 8xR-CHOP-14 (n=306). After a median obs time of 82 mo, the estimated 7-yr OS rates were 50% for 6xCHOP-14, 52% for 8xCHOP-14, 62% for 6xR-CHOP-14, and 60% for 8xR-CHOP-14. In a multivariate analysis using 6xR-CHOP-14 without R as the reference and adjusting for the stratification variables elevated LDH, stage III&IV, ECOG ps>1, bulky dis, >1 extranodal site, and age >70, both R arms had a significantly improved EFS (6xR-CHOP-14: RR=0.5, p<0.001; 8xR-CHOP-14: RR=0.5, p<0.001), PFS (6xR-CHOP-14: RR=0.5, p<0.001; 8xR-CHOP-14: RR=0.5; p<0.001) and OS (6xR-CHOP-14: RR=0.6; p<0.001; 8xR-CHOP-14: RR=0.7; p=0.004). 6xR-CHOP-14 was slightly better than 8-R-CHOP-14 with respect to all endpoints and had a significantly better OS in pts with bulky dis (p=0.005). Conclusions: In contrast to the 3-yr FU, not only 6xR-CHOP-14, but also 8xR-CHOP-14 achieved a significantly better OS compared to 6xCHOP-14 after a med obs time of 82 mo. Due to its lower tox and shorter time under CTX (6xCHOP-14: 10 wks, 8xCHOP-14: 15 wks, and 8x-CHOP-21 even 21 wks, each plus 1 d), 6xCHOP-14 in comb with 8 app of R is the preferred regimen for elderly patients with CD20+ DLBCL. The significant superiority of 6xR-CHOP-14 over 8xR-CHOP-21 in pts with bulky dis, who received RX to the resp areas, suggests that RX to bulky dis is more effective when given after 6 than after 8 cy of R-CHOP-14.
Extended neoadjuvant chemotherapy (CT) in borderline resectable pancreas cancer (BRPC): Is preoperative chemoradiation (CRT) essential?
Authors: Vincent J. Picozzi, Flavio G. Rocha, J. Bart Rose, L. William Traverso, Adnan Alseidi, Bruce S. Lin, Thomas A. Biehl, John A. Ryan, Ravi Moonka, Scott Helton
Journal: Journal of Clinical Oncology (2013)

236 Background: The optimum approach to maximize R0 resection rate in BRPC is unknown. We evaluated an approach in BRPC using extended duration neoadjuvant CT, typically without neoadjuvant CRT to assess R0 resection rate on an "intent to treat"basis. Methods: Patients (pts) were identified from a prospectively-maintained database from 2008-2012. Pts required (1) BRPC per radiographic staging using NCCN/AHPBA criteria, (2) no prior PC therapy (rx) PC, (3) negative staging laparoscopy prior to rx, and (4) all cancer rx at VMMC prior to decision on "downstaging" surgery (S). Pts were initially treated with gemcitabine/docetaxel CT until (a) disease progression, or (b) 24 weeks (wks), before assessment for local rx. Pts with systemic progression and/or inability to complete 24 wks of CT were excluded from local rx; pts with localized cancer at 24 wks judged unlikely to achieve R0 resection were offered 5FU-based CRT then reassessed; all other pts were offered S. Results: Of 70 identified pts, 12/70 (17%) are on initial CT; 58 are fully evaluable. 51/58 pts (88%) completed 24 wks of CT. Response rates to CT were (a) serologic 42/58 (72%) &gt; 50% decline in baseline CA19.9 (median 85%), and (b) radiographic of 47 pts evaluable by RECIST, PR/SD/PD were 60%/32%/8% respectively. 14/58 pts (24%) did not receive local rx (7 intercurrent illness, 7 disease progression). 44/58 pts (76%) were offered local rx- 12/58 (21%) CRT and 32/58 (55%) S. 2 pts receiving CRT later underwent S. CRT. 29 pts (50% total evaluable pts, 85% pts undergoing S) achieved R0 resection;10/29 pts (35%) via en bloc venous resections. 5 pts were inoperable (3 local - subsequently given CRT, 2 systemic). At median f/u of 16 mo, 21/29 (72%) R0 resection pts remain disease free (range 7+-47+mo) along with 4/12 pts (33%) receiving CRT w/o R0 resection (range 12+ -30 mo). 25/58 (43%) fully evaluable pts remain progression free on an "intent to treat" basis. Median OS for all pts is 27 mo (95% CI 15-39 mo); 25/29 R0 resected pts remain alive ( median OS&gt; 20 mo). Conclusions: (1) extended neaoadjuvant CT is a feasible approach in BRPC. (2) Gemcitabine/docetaxel has significant activity in localized PC. (3) Neoadjuvant CRT may not be essential to R0 resection in BRPC.
Mutational analysis of locally advanced rectal cancer and response to neoadjuvant chemoradiation.
Authors: Andrea Lyn Russo, David P. Ryan, Darrell R. Borger, Jennifer Yon-Li Wo, Jackie Szymonifka, Eunice Lee Kwak, Lawrence Scott Blaszkowsky, Jeffrey W. Clark, Jill N. Allen, Andrew X. Zhu, David L. Berger, James C. Cusack, Kevin M. Haigis, Theodore S. Hong
Journal: Journal of Clinical Oncology (2013)

449 Background: Preoperative chemoradiation (CRT) is the standard of care for locally advanced rectal adenocarcinoma and leads to pathologic complete response (pCR) rates of 8-20%. pCR has been correlated with improved long term outcomes. Known mutations may contribute to lack of pCR. We retrospectively evaluated our single institution experience to determine rates and potential mutational and clinical predictors of pCR. Methods: With IRB approval, we reviewed 79 consecutive patients with stage II/III rectal adenocarcinoma, diagnosed from 7/2005–6/2010. Patients received preoperative CRT to 50.4 Gy and concurrent 5-FU based chemotherapy prior to total mesorectal excision. Primary endpoint was pCR rate by Dworak tumor regression grade. Mutations were analyzed on pre- and/or post-treatment tissue available for 47 patients with a multiplexed clinical assay on nucleic acid (SNaPshot), which tests for 130 mutations across 15 cancer genes. 32 patients did not have enough tissue for analysis. Other variables including T/N stage, grade, circumferentiality, distance to anal verge, tumor size (continuous, per cm), pre and post-CRT CEA levels, and treatment duration were evaluated using logistic regression analysis. Results: Median age was 58 years and 85% had stage III disease. Among 54% of patients with mutations assessed, the following were present: 37% KRAS, 3% APC, 3% BRAF, 5% NRAS, 4% PIK3CA, 8% TP53. TP53 testing was limited to common mutation sites. In the entire cohort, 20% had a pCR. No patients with BRAF, NRAS or KRAS mutations had a pCR. Patients with a pCR were more likely to have a post-RT CEA ≤ 2.5 (93% vs 62%, p=0.002) and no mutations identified (100% vs 38%, p=0.019). pCR patients had a trend to lower rates of KRAS mutations (0% vs 41%, p=0.1). On UVA, predictors of pCR included: post-RT CEA ≤ 2.5 (OR 8.6, 95% CI 1.03 – 71.9, p=0.047), insufficient tissue to analyze (OR 5.1, CI 1.45-18, p=0.011), and smaller tumor size (OR 0.69, CI 0.48 – 1.0, p=0.05). With a median follow-up of 30 months, there were 3 local and 6 distant recurrences. None with a pCR developed recurrence. Conclusions: Patients with the composite characteristics of being BRAF, KRAS, and NRAS wild type rectal cancer are more likely to have a pCR with preoperative CRT.
Venothromboembolism and radical cystectomy: Prevalence of risk factors and comparison of anticoagulation use.
Authors: Andrew Sun, Hooman Djaladat, Anne Schuckman, Gus Miranda, Siamak Daneshmand
Journal: Journal of Clinical Oncology (2014)

339 Background: Radical cystectomy is a major pelvic surgery associated with relatively high rates of venothromboembolism (VTE). This study focuses on prevalence of known risk factors in patients undergoing radical cystectomy who suffered a symptomatic VTE and compared use of warfarin and heparin in prophylaxis. Methods: We conducted a retrospective review of 2,730 patients who underwent open cystectomy at USC between 1971-2012 using the IRB approved bladder cancer database. Patients who suffered VTE during the peri-operative period were identified. Preoperative, operative, and postoperative risk factors for VTE were analyzed. Data on use of anticoagulation was obtained and used to compare a historical cohort of warfarin use as prophylaxis (1971-2007) to the modern cohort of subcutaneous heparin use (2009-2012). A Chi-squared test was used to determine significance of any differences in prophylaxis use. Results: A total of 129 patients (4.7%) with symptomatic VTE were identified. 112/129 (86.8%) fit intent to cure inclusion criteria and were further evaluated for demographic information (85% male, median age 69.9, median BMI 27.9, and smoking history in 61.6%) and risk factors. Of pre-operative VTE risk factors, previous chemotherapy (9.8%) and other active medical illness (17.4%, e.g. atrial fibrillation, hypothyroidism, congestive heart failure) were most common. Median operative time was 363 minutes; median EBL was 800 ml with median transfusion of 2.0 units of PRBCs. The median day of first ambulation was POD 3, median LOS was 11 days, and a median interval between surgery and VTE diagnosis was 20.5 days. 15.1% of VTE patients also had a post-op infection. Of the 129 VTE cases, the overall rate from 1971-2007 (treated with warfarin) was 4.1%, while the rate from 2009-2012 (treated with heparin) was 6.3% (p=0.054). Percent of patients with a VTE occurring after discharge from 1971-2007 and 2009-2012 were 2.3% and 4.1%, respectively (p=0.052). Conclusions: Most VTEs occur after discharge, indicating a possible need for VTE prophylaxis beyond the immediate post-op period. There was a trend toward reduced risk of VTE with post-operative use of warfarin compared to heparin.
Correlation of tumor-associated macrophages with clinicopathologic factors and angiogenesis in gastric cancer.
Authors: Sung-Jig Lim, Sung Il Choi, Jae Park
Journal: Journal of Clinical Oncology (2014)

54 Background: Tumor associated macrophages (TAMs) are major components of tumor environment, and polarized into M1 and M2 type. M1 has been known as antitumorigenic, whereas M2 as protumorigenic. M2 have a significant role in tumor progression by promoting tumor cell invasion, migration and angiogenesis. We evaluated the M2 macrophages to investigate its importance in predicting clinical outcome or prognosis, and the relationship between M2 and angiogenesis in patients with gastric cancer. Methods: Formalin-fixed, paraffin-embedded blocks were obtained from the 88 patients with gastric cancer. CD163+ TAMs and CD105+ vessels were evaluated by immunohistochemical staining and the extent of CD163+ TAMs in tumor were divided into three groups: (A) infiltrated TAMs in cancer cell nest (nest TAMs); (B) infiltrated TAMs in tumor stroma (stroma TAMs); and (C) infiltrated TAMs along the invasive margin of a tumor (margin TAMs). Results: The increased stroma and margin TAMs (&gt;72 and &gt;102, respectively) were closely correlated with lymph node metastasis, TNM stage and lymphatic invasion (p&lt;0.05 in 3 factors) and positive correlation existed between the stroma and margin TAMs (p&lt;0.001). Disease-free survival rate analyzed using the Kaplan– Meier method was significantly lower in patient with high stroma and margin TMAs than patient with low stroma and margin TAMs (p=0.0039 and 0.0499, respectively). CD105+ vessels showed significant correlation with lymph node metastasis and lymphatic invasion.(p=0.006 and p&lt;0.0001, respectively) Stromal, marginal and nest TAMs were positively correlated with CD105+ vessels (p=0.001). Conclusions: M2 infiltration in tumor stroma and tumor margin in gastric cancer showed relationship with aggressive phenotypes such as lymph node metastasis, TNM stage and lymphatic invasion and was correlated with angiogenesis. This study supports the view that the adverse prognostic impact of M2 involves tumor angiogenesis in gastric cancer.
Androgen deprivation therapy (ADT) and physical function in men with nonmetastatic prostate cancer
Authors: H. Breunis, M. Leach, G. Naglie, I. F. Tannock, N. E. Fleshner, M. Krahn, S. Duff-Canning, G. Tomlinson, P. Warde, S. M. Alibhai
Journal: Journal of Clinical Oncology (2008)

5130 Background: Although prolonged use of ADT is hypothesized to adversely affect physical function, few studies have actually examined this relationship using objective measures of physical function. Methods: Men age 50 or older with non- metastatic prostate cancer (PC) who were starting continuous ADT were enrolled in this prospective longitudinal study. Physical function was assessed with the six-minute walk test (6MWT), grip strength, and the Timed Up and Go (TUG) test, representing endurance, upper extremity strength, and lower extremity strength, respectively. Assessments were done at baseline, 3 months, 6 months, and 12 months. Two control groups, matched on age, education, and baseline function were also enrolled. One control group had PC but did not receive ADT, and the other group did not have PC. Results: 88 patients on ADT, 86 PC controls, and 86 healthy controls were enrolled. All three groups were similar in age (mean age 69.1 y for the cohort (range 50–87)). At baseline, all three groups had similar 6MWT, grip strength, and TUG scores (all ANOVA p>0.05) and most patients reported excellent health and functional status. The 6MWT improved in both control groups (p=0.003 and 0.007 for PC and healthy controls, respectively) but remained stable in the ADT group (p=0.269)). Grip strength declined sharply in the ADT group by 3 months and declined further at 12 months (40.1 kg at baseline; 37.9 kg at 3 months and 37.5 kg at 12 months, p<0.001). A much smaller, more gradual decline was seen in the PC control group (41.8 kg at baseline, 41.7 kg at 3 months, and 41.1 kg at 12 months, p=0.013), while the healthy control group remained stable (p=0.739). There was a trend toward worsening TUG scores in the ADT group (p=0.075) but TUG scores were unchanged in both control groups (p>0.10). Conclusions: Endurance and upper extremity strength are affected within 3–6 months of starting ADT. Declines persist at 12 months. Lower extremity strength may also be affected but the TUG may not be sufficiently sensitive in this relatively healthy cohort. Intervention studies of endurance or resistance exercise to counteract loss of physical function in this cohort are warranted. No significant financial relationships to disclose.