tbuckley/cabot-search huggingface dataset:
Differential alteration of TRAIL and its receptor expression profiles in patients with pancreatic ductal adenocarcinoma
Authors: A. D. Sanlioglu, E. Dirice, O. Elpek, A. F. Korcum, M. K. Balci, A. Omer, T. S. Griffith, S. Sanlioglu
Journal: Journal of Clinical Oncology (2008)

15607 Background: High levels of TRAIL DcR2 expression has recently been correlated with high Gleason scores, PSA recurrence and decreased survival in patients with prostate carcinoma. However, the importance of TRAIL and its receptor expression in respect to carcinogenesis process including pancreas is not known. This study reveals the expression profile of TRAIL and its receptors in pancreatic tissues of both non-cancer patients and patients with pancreatic ductal adenocarcinoma. Methods: Thirty one non-cancer patients and thirty-four patients with pancreatic ductal adenocarcinoma totaling up to sixty-five patients were included in the study. TRAIL and its receptor profiles were determined by immunohistochemistry. Intensity and distribution of antibody staining were combined to get the final immune-staining scores for each patient. Tumor grade, tumor stage, tumor diameter, perineural invasion, number of lymph-node metastasis were used for comparison purposes. The statistical significance among the groups was assessed by Kruskal Wallis followed by Mann Whitney U test. The correlation significance was revealed by Spearman's Rho analysis. Results: TRAIL decoy receptor-2 (DcR2) and death receptor-4 (DR4) expressions were up-regulated in patients with pancreatic ductal carcinoma compared to non-cancer patients. In addition, pancreatic cancer patients exhibited higher levels of DcR2 but lower levels of DR4 expression in aciner cells. Higher levels of DcR2 expression were also observed in Langerhans islets of pancreatic cancer patients. Conclusions: Differential alteration of TRAIL and its receptor expression profiles in patients with pancreatic adenocarcinoma suggest that TRAIL and its receptors may play pivotal roles during pancreas carcinogenesis. No significant financial relationships to disclose.
Reduced thromboembolic events with DN-101 (high-dose calcitriol) treatment of androgen-independent prostate cancer: Hypothesis for a new class of anticoagulants
Authors: P. M. Venner, C. Ryan, D. P. Petrylak, G. S. Chatta, J. Ruether, K. N. Chi, J. Curd, T. M. Beer
Journal: Journal of Clinical Oncology (2006)

4505 Background: Thromboembolic events (TEs) occur at an increased rate in patients with advanced malignancies including androgen-independent prostate cancer (AIPC). DN-101, a new high-dose oral formulation of calcitriol (1,25-dihydroxycholecalciferol), is the active form of Vitamin D and the natural ligand for the nuclear receptor VDR. Calcitriol upregulates thrombomodulin, a natural anticoagulant, and downregulates tissue factor, a procoagulant both in vitro and in vivo. Further, VDR knockout mice demonstrate increased susceptibility to thrombosis. ASCENT is a double-blind, placebo-controlled study in 250 men with metastatic AIPC. Efficacy results have been previously reported (ASCO, 2005). Methods: 250 patients were randomized 1:1 to docetaxel 36 mg/m 2 plus 45 μg DN-101 weekly or to the same docetaxel regimen plus placebo. In this exploratory analysis the incidence of TE (defined as deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), cerebrovascular accident (CVA) and arterial thrombosis (AT)) in the two study groups was compared using the Fisher’s exact test. Results: There were fewer patients with serious adverse events (SAEs) in the DN-101 group than in the placebo group (27 % vs. 41%). As shown in the table , DN-101 treated patients experienced fewer TEs including fewer TE SAEs, Grade 3 or 4 TEs and all grade TEs. No imbalance in baseline use of anticoagulants was observed. Conclusions: The well-described effects of calcitriol on protein components of the coagulation cascade provide a biologic basis for the observed reduction in thromboembolic events in the DN-101 treated patients. This hypothesis should be tested prospectively in future studies of DN-101. [Table: see text] [Table: see text]
Comparison of ColoPrint risk classification with clinical risk in the prospective PARSC trial.
Authors: Ramon Salazar, Jaume Capdevila, Robert Rosenberg, Jan Willem de Waard, Bengt Glimelius, Frederic Bibeau, Joost Klaase, Jacobus JM Van der Hoeven, Rachel A Midgley, George J. Chang, Thomas Bachleitner-Hofmann, Michio Asano, Reinhard Ziebermayr, Edward Allen Levine, Kenneth B. Deck, Jamie Sington, Wai Lun Law, Imad Shbeeb, Lisette Stork, John Marshall
Journal: Journal of Clinical Oncology (2014)

465 Background: The 18-gene expression profile, ColoPrint, has been developed and validated for identifying risk of recurrence in patients with early-stage colon cancer (CC). In a pooled stage II validation study ColoPrint identified 63% of patients as Low Risk with a 3-yr recurrence-free survival (RFS) of 93% while High Risk patients had a 3-yr RFS of 82% with a HR of 2.7 (p=0.001). PARSC is a prospective study for the assessment of recurrence risk in stage II CC patients using ColoPrint. ColoPrint classification is compared to NCCN risk classification. Methods: The study enrolled 468 patients with histologically proven stage II CC from 31 institutes in Europe, the United States, and Asia between October 2008 and May 2013. Synchronous tumors were excluded. ColoPrint results were not disclosed to the physician and patient. Treatment was at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative. A McNemars test is performed to compare ColoPrint with NCCN risk classification. A p value ≤ 0.05 indicates the two tests differ significantly. Results: ColoPrint classified 320 (68%) patients as Low Risk and 148 (32%) as High Risk. 89 patients (19%) received adjuvant chemotherapy. In the ColoPrint Low Risk group, 57 (18%) patients received adjuvant chemotherapy while 32 (22%) of ColoPrint High Risk patients received chemotherapy. According to NCCN high risk factors (T4, high grade (exclusive of MSI-H), lymphovascular/perineural invasion, perforation/obstruction, &lt;12 nodes examined, positive margins) 234 (50%) patients were NCCN Low Risk and 234 were NCCN High Risk. 72 (31%) of the NCCN Low Risk patients are ColoPrint High Risk. 158 (68%) of the NCCN High Risk patients are ColoPrint Low Risk. MSI-status was assessed in 86 (18%) patients of which 29 were MSI high and 57 were MSS. All MSI high were classified as ColoPrint Low Risk. Conclusions: The PARSC study is the first prospective study to compare genomic and clinical risk assessment and we observed marked differences between NCCN risk classification and ColoPrint. The clinical validity of these methods will be based on the outcomes at 3 and 5 years. Clinical trial information: NCT00903565. [Table: see text]
Evaluation of TOP2A and TIMP-1 as predictive markers of pathologic complete response to neoadjuvant anthracycline-based chemotherapy.
Authors: Joyce Maria L. Maia, Elizabeth Santana Santos, Rafael Costa Lessa, Felipe D'Almeida Costa, Stephania Bezerra, Rafael Malagoli Rocha, Carlos Frederico Lopes Benevides, Vladmir C. Lima, Adriana Regina G. Ribeiro, Marcello Ferretti Fanelli, Alexandre Andre Balieiro Anastacio da Costa, Celso Abdon Mello
Journal: Journal of Clinical Oncology (2013)

e11503 Background: Factors predictive of response to anthracyclines can help selecting patients who really benefit from its use. HER2 amplification, TOP2A aberrations, and changes in tissue inhibitor of metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline chemotherapy. Methods: We retrospectively analyzed data on the outcome of patients undergoing neoadjuvant anthracycline-based chemotherapy. Evaluated nuclear TOP2A protein expression and cytoplasmatic TIMP-1 expression in tumor cells in breast cancer biopsies by immunohistochemistry (IHC) and reviewed the pathological responses after completion of neoadjuvant treatment. Results: From 2002 to 2012, data from 97 patients was reviewed. Sixty four patients had the paraffin blocks corresponding to the pre-treatment biopsy to analysis the TOP2A and forty nine to TIMP-1. Patients were considered positive for TOP2A if the level of expression in IHC was higher than 20% and graduated TIMP-1 as weak, moderate or strong expression. Thirty percent of the patients achieved pathologic complete response (pCR) in pos-treatment surgical specimens. There was an association between TOP2A IHC expression and tumor pathological complete response (pCR) with higher pCR in TOPO2A positive tumors (pCR 44% vs 14%; p=0.008). There was no association between TIMP-1 expression and pCR. A moderate or strong TIMP-1 expression was associated with higher disease-free survival in multivariate analysis (p=0,005). No difference in PFS and OS was observed between patients with pCR after a median follow-up of 36 months. Conclusions: The expression of TOP2A seems to be a promising predictive biomarker of pCR to antracycline-based neoadjuvant chemotherapy in HER2 breast cancer. The predictive value and form of assessment of TIMP-1 remain uncertain. These findings should be better evaluated in prospective neoadjuvant trials.
IP catheter complications and associated risk factors in patients with ovarian cancer
Authors: K. Long, R. Malik, J. P. Curtin, B. Pothuri
Journal: Journal of Clinical Oncology (2008)

5525 Background: Recent data suggests that intraperitoneal (IP) chemotherapy improves survival over IV chemotherapy in the initial treatment of ovarian cancer. We sought to explore the utilization, complications, and risk factors for intraperitoneal catheter complications in ovarian cancer patients undergoing IP chemotherapy. Methods: This study is a retrospective review of patients undergoing IP catheter placement and subsequent IP chemotherapy at our medical center from July 2000 to February 2007. Standard chi-square statistical analysis was utilized. Results: We identified 51 patients with ovarian cancer who underwent IP chemotherapy during this time period. Median age was 57 (range 36–74). Median BMI was 24.6 (range 17.7–41.3). Thirty-six patients (70.6%) were undergoing secondary treatment and 13 (25.4%) were undergoing primary treatment. Each patient received a platinum agent in addition to Taxol, Topotecan, FUDR, or Doxil. A total of 9 patients (17.6%) were identified as having IP catheter complications: 3 patients (5.8%) had peritonitis and 6 patients (11.8%) had IP catheters that were malpositioned and/or leaking. All 3 patients with peritonitis required removal of the catheter, hospitalization, and IV antibiotics. Of the 6 patients with malpositioned/leaking catheters, 3 required removal and 3 required revision of the catheter. Of the 9 patients with complications, 2 had hyperlipidemia, 1 had hypertension, and none had diabetes. Two of the 9 patients (22%) with IP catheter complications completed the scheduled regimen of chemotherapy, while 27 of 42 patients (64%) without IP catheter complications were able to complete their treatment regimen (p<.05). We noted that obesity, defined as a body mass index greater than 30, was associated with a higher incidence of IP catheter complications with a P<.001. There was no significant difference in IP catheter complications between patients receiving primary and secondary treatment. Conclusion: The majority of IP catheter complications are related to infection or catheter malfunction, with obesity being a significant risk factor for the development of those complications. In addition, patients with IP catheter complications have a significantly lower rate of completion of their chemotherapy regimens. No significant financial relationships to disclose.
Using palliative care to maximize the value of care for patients with advanced cancer.
Authors: Risha Gidwani, Randall Gale, Diane E. Meier, Steven M Asch
Journal: Journal of Clinical Oncology (2014)

59 Background: Cancer is one of the highest cost conditions in the United States, with growth in cancer costs outpacing general medical costs. This is troubling from a patient perspective. Patients with cancer experience significantly greater financial burdens compared with patients with other medical conditions. Many patients forgo or discontinue cancer treatment partly because they do not want to burden their families with significant debt. The growth of cancer and other medical costs is also threatening the health of the U.S. economy, prompting calls for the need for high-value practices. In healthcare, value indicates an achievement of patient outcomes proportional to the resources spent to achieve them. Increasing the provision of palliative care may be one way to achieve higher value care in cancer. Methods: We summarize the literature regarding palliative care, patient outcomes, and costs to assess the value of palliative care in advanced cancer. We also review the literature to identify reasons for low patient receipt of palliative care. Results: Palliative care represents a strong opportunity to improve the value of cancer care. Palliative care is associated with better informed and more satisfied patients and families, a reduction in use of undesired medical services, and does not pose a risk of increased mortality. Reasons for low rates of palliative care include a mismatch between how patients perceive palliative care and how physicians believe patients perceive palliative care, a lack of familiarity with locally-available palliative services, and a perceived incompatibility with cancer therapy. Conclusions: Palliative care for patients with cancer can improve the patient and family experience while maximizing value for the healthcare system and averting unnecessary patient financial burden. Systems redesign is needed in order to support oncologists in supporting the palliative care needs of their patients and realizing this high-value cancer care.
Comparison of docetaxel and vinca alkaloid, alone or in combination with other chemotherapy agents, in the first-line treatment of advanced non-small cell lung cancer (NSCLC): A meta-analysis
Authors: J. Y. Douillard, F. Fossela, V. Georgoulias, J. L. Pujol, K. Kubota, A. Monnier, K. Takeda, M. Cucherat, S. Laporte
Journal: Journal of Clinical Oncology (2006)

7034 Background: Taxanes and vinca alkaloids are commonly used agents, in first-line therapy of advanced NSCLC. As some data in comparative studies have suggested possible differences in survival and safety, we performed a meta-analysis in order to assess the potential benefit of docetaxel-based regimens in comparison with vinca alkaloid-based regimens, in terms of overall survival (OS) and toxicity. Methods: MEDLINE, CANCERLIT and Cochrane Library searches were supplemented by information from clinical study reports and by manual searching of relevant meeting proceedings. Only randomized trials comparing docetaxel-based chemotherapy to vinorelbine- or vindesine-based chemotherapy were included. Outcomes recorded were OS and neutropenia. Fixed-effects and random-effects models were used to estimate the pooled hazard ratio (HR) of OS and the odds ratio (OR) of neutropenia. A HR or OR less than 1 indicates that docetaxel is superior to vinca alkaloids. Heterogeneity was assessed using the Cochran Q-test. Results: The seven selected trials (six using vinorelbine as vinca alkaloid) yielded a total of 2,867 patients (docetaxel regimens: 1,638; vinca alkaloid regimens: 1,229). Docetaxel was combined with a platinum compound in three trials, with gemcitabine in two trials and used as monotherapy in two trials. The vinca alkaloid was combined with a platinum compound in six trials, and used alone (vinorelbine) in one. The pooled estimate of the OS shows a significant improvement in favor of docetaxel (HR=0.89, 95%CI [0.82;0.96], p=0.03), this benefit persisting after exclusion of the vindesine study (HR=0.90 [0.83;0.98]) and also after excluding monotherapy regimens (HR=0.89 [0.82;0.97]. While neutropenia was common, it was significantly less frequent with docetaxel (OR=0.60 [0.39;0.92], p=0.019), as was febrile neutropenia (OR=0.60 [0.39;0.96], p=0.034). Conclusions: The results of this meta-analysis support the superior efficacy (OS) and safety (neutropenia and febrile neutropenia) of docetaxel in first-line therapy of advanced NSCLC as compared with vindesine or vinorelbine. Detailed results, as well as subgroup analyses, will be presented at the meeting. [Table: see text]
A single institution analysis of treatment outcomes in pancreatic cancer through the decade
Authors: R. Katipamula, A. Conrad, S. Emani, K. Seetharaman
Journal: Journal of Clinical Oncology (2004)

4241 Background: Despite advances in therapies for PancrCa, improvement in survival has been difficult to establish. Methods: A retrospective chart review of 204 consecutive patient with PancrCa presenting between 1990–2001 at Saint Vincent Hospital was done and the data obtained was analyzed for significaance using student t-test. Results: Of the 204 patients there were 103 males and 101 females. The age at diagnosis ranged from 33 to 93 years (mean=69, 95% CI=68,71). Of the 204 patients, 174 (85%) were already in stage 4 at diagnosis. In the cohort, 28 (14%) received Whipple surgery, 24 (12%) received 5-FU as first line treatment, 23 (11%) received Gemzar as first line treatment, and 23 (11%) received a second line treatment. Survival data was available on 195 of the 204 patients. The median survival for the 195 patients was 3.5 months and mean survival was 6.8 months (95% CI=5.5,8.1). For males, the median survival was 4.3 months and mean survival was 8.4 months (95% CI=6.1,10.7). For females, the median survival was 3.1 months and mean survival was 5.1 months (95% CI=3.9,6.3). Length of survival was greater in males than females (t=2.46, p=0.01). Length of survival for patients undergoing surgery (mean=12, 95% CI=6.7,17.3) was greater than that for patients not undergoing surgery (mean=6, 95% CI=4.7,7.3; t=3.00, p=0.003). Patients receiving 5-FU as first line treatment, had mean survival of 7.5 months (95% CI=4.4, 10.7), and patients receiving Gemzar as first line treatment had mean survival of 7.8 months (95% CI=3.1, 12.5). Patients receiving second line and experimental treatments had a mean survival rate of 15 months (95% CI=10.6, 19.8). Conclusions: Female patients had a poor prognosis compared to male patients. The introduction of newer chemotherapeutic agents in the last few years in the treatment of pancreatic cancer has improved the survival by a few months. However, being retrospective study observations could not be made on patient's quality of life. Supported by an educational grant from Eli Lily Pharmaceuticals. No significant financial relationships to disclose.
Correlation of concurrent lobular neoplasia (LN) and ipsilateral breast cancer recurrence in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving therapy (BCT)
Authors: U. Rudloff, E. Brogi, J. P. Brockway, C. A. Wynveen, T. Nehhozina, A. Reiner, S. Patil, K. J. Van Zee
Journal: Journal of Clinical Oncology (2008)

585 Background: Multiple clinicopathologic factors have been analyzed for their association with an increased risk of ipsilateral breast tumor recurrence (IBTR) following conservative surgery for DCIS. The incidence of proliferative lesions, such as atypical ductal hyperplasia (ADH), columnar cell changes (CCC), and lobular neoplasia (LN) associated with invasive and non-invasive breast cancer has been reported to be as high as 23%, however, the relevance of these lesions with respect to the natural history of DCIS and the risk of IBTR remains unknown. Methods: 297 patients with DCIS managed with BCT at our institution from 1991 and 1995 were identified from our institutional database. Pathology slides from all cases were retrieved, or prepared from tissue blocks if the original slides were unavailable. Histologic sections from each case were reviewed by a dedicated breast pathologist with particular attention to the presence of LN, ADH, and CCC. Actuarial 5-, 10-, and 15-year local recurrence rates were calculated by the Kaplan-Meier method and compared with the log-rank test. Results: Concurrent LN was present in 43 of 297 patients (15%), ADH in 37 (13%), and CCC in 71 (24%). Median follow-up time was 11.5 years. IBTR occurred in 40 of 225 patients (18%) without LN versus 15 of 43 (35%) with LN (p<0.006; HR 2.35). 5-, 10-, and 15-year cumulative incidence rates of IBTR were twice as high in women with DCIS and LN compared to DCIS alone (Table). Concomitant ADH (HR 1.54) and CCC (HR 1.25) were not significantly associated with IBTR (p=0.20 and p=0.43, respectively). Conclusions: Concurrent LN significantly increases the risk of IBTR in women with DCIS treated with BCT. Further study of risk reducing strategies for women with DCIS associated with LN is necessary. Cumulative Incidences and Hazard Ratios for Ipsilateral Breast Tumor Recurrence by Presence of Concurrent Proliferative Lesion 5-year Cumulative Incidence (CI) 10-year Cumulative Incidence (CI) 15-year Cumulative Incidence (CI) Hazard Ratio ¶ P-value No LN 12% (8;17) 19% (13; 24) 25% (17; 32) 1 LN 25% (11;39) 38% (21; 54) 51% (30; 72) 2.35 < 0.006 No ADH 14% (9;19) 21% (16; 27) 28% (20; 36) 1 ADH 22% (7;36) 25% (10; 41) 41% (21; 61) 1.54 0.20 No CCC 16% (10;21) 21% (15; 28) 27% (19; 35) 1 CCC 15% (6;24) 24% (13; 35) 37% (22; 53) 1.25 0.43 CI - Confidence intervals; ¶ Hazard ratios obtained from the Cox proportional hazards model. All other estimates derived using the Kaplan-Meier method No significant financial relationships to disclose.
Phase I study of the PARP inhibitor olaparib (O) in combination with carboplatin (C) in BRCA1/2 mutation carriers with breast (Br) or ovarian (Ov) cancer (Ca).
Authors: J. Lee, C. M. Annunziata, L. M. Minasian, J. Zujewski, S. A. Prindiville, H. L. Kotz, J. Squires, N. D. Houston, J. J. Ji, M. Yu, J. H. Doroshow, E. C. Kohn
Journal: Journal of Clinical Oncology (2011)

2520 Background: The PARPi O has single-agent activity against BRCA1/2 mutation carriers (Br/Ov mut+) Br/OvCa. We hypothesized addition of C to O to stress the DNA repair machinery would further improve this clinical benefit. Methods: A 3x3 dose escalation (NCT00647062) incorporated daily oral O at 100 or 200 mg q12h (dose level [DL] 1/2) with IV C AUC3 on day 8 then every 21d; DL6-9 gave O d1-7 at 200 then 400mg q12h, with C AUC 3 on d2 then escalation to AUC5 (no DL3-5). No more than 8 O/C cycles were given, then O was taken daily until progression. Safety was assessed every cycle and response assessed every other cycle. PBMCs were collected preC1, d3 or d7, and prior to C2 for PARP activity measured by a PAR incorporation ELISA. Results: 30 women (26 serous Ov/4 Br) were treated on 6 DLs. All OvCa pts were previously exposed to platinum (from last platinum 6-55mos, median=14). DLT was thrombocytopenia and delayed neutropenic recovery (DL2: O 200 mg q12h/C AUC3 [2/5 pts]). MTD was not reached. RP2D is DL9, O 400mg q12h d1-7 with C AUC5 [1/6 DLT, delayed marrow recovery]. Gr 3/4 AEs included anemia (10%), thrombocytopenia (20%), neutropenia (17%), fatigue (3%) and C hypersensitivity (13%). 6 pts prematurely discontinued C due to either allergic reaction (4) or myelosuppression (2). 3 pts with C AUC5 required PEG-filgrastim on at least 1 cycle. Of 27 evaluable pts, PR was seen in 8/23 OvCa pts (4-24 cycles) and 3/4 BrCa pts (2 TNBC; 1 ER/PR+; 6-8 cycles); stabilization occurred in 11/23 OvCa pts (4-24 cycles) and 1 BrCa pt (10 cycles): clinical benefit 83% OvCa, 4/4 BrCa. PBMC PAR concentrations were markedly reduced with O at all DL. A subset of women had rebound of PAR incorporation prior to cycle 2 (p=0.0027). This did not correlate with frequency or duration of response. Conclusions: O 400 mg bid d1-7 with C AUC4/5 q21d is active and tolerable in Br/OvCa mut+ pts. Interactive marrow suppression was observed. An expansion cohort in Br/Ov mut+ pts nears accrual completion; paired tumor biopsies and PBMCs will be used to measure DNA damage endpoints and biomarkers. Patient cohorts with low probability of BRCA mutation TNBC and high-grade serous OvCa continue dose escalation.