tbuckley/cabot-search huggingface dataset:
Circulating tumor cells in adjuvant breast cancer patients
Authors: S. Almokadem, K. Leitzel, H. A. Harvey, E. Bannon, S. M. Ali, C. Miller, M. Repollet, W. J. Allard, L. W. W. M. Terstappen, A. Lipton
Journal: Journal of Clinical Oncology (2005)

667 Background: One of the first steps in metastasis is the ability of primary breast cancer cells to detach and invade the circulation. The presence of ≥5 circulating tumor cells (CTCs) in 7.5 mL blood from metastatic breast cancer patients predicts shorter progression-free and overall survival (M Christofanilli et al NEJM 351:781–791, 2004). The purpose of our study was to determine if CTCs were present in the blood of patients who had recently completed adjuvant chemotherapy. Methods: Blood was obtained from 33 breast cancer patients within 12 months after completing adjuvant chemotherapy. No patient had evidence of metastatic cancer on imaging. CTCs were immunomagnetically separated and fluorescently stained with the CellSearch Kit. Cells were classified using the CellSpotter Analyzer as CTCs if they stained positive for DAPI (nuclear dye), and cytokeratin 8, 18 and/or 19, and if they stained negative for the leukocyte-specific antibody CD45. Results: In a control group of 145 healthy females, 8 (5.5%) had 1 CTC/7.5 mL blood. In 199 patients with benign disease, 14 (7.0%) had 1 CTC/7.5 mL, and only 1 (0.5%) had 3 CTCs/7.5 mL detected in their blood. Of the 33 total patients in this study, 3 patients (9.1%) had ≥1 CTC/7.5 mL detected in their blood samples (one patient had 1 CTC in one 7.5 mL tube, and another patient had 2 CTCs in one 7.5 mL tube. The second 7.5 mL tube from both of these patients had no CTCs. The third patient had 1 CTC in three of the four 7.5 mL tubes tested). In the other 30 patients, no CTCs were detected (0/4 tubes in 16 patients; 0/2 tubes in 14 patients). In summary, CTCs were detected in 3/33 (9.1%) adjuvant breast cancer patients, 8/145 (5.5%) healthy controls, and 15/199 (7.5%) benign disease patients. There were no significant differences in the proportion of CTCs between these groups (p≥0.30, Fisher’s exact test). Of 6 patients with 3+ IHC for HER-2/neu in the primary tumor, 2 (33%) had CTCs in their blood. Conclusions: No significant difference in the proportion of CTCs detected was observed between breast cancer patients who recently completed adjuvant chemotherapy and the control groups. Patient accrual and follow-up in this study continues to determine if the presence of elevated CTCs is associated with early recurrence of the disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Immunicon
The effect of therapeutic anticoagulation on overall survival (OS) in men receiving docetaxel chemotherapy for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Caroline F. Pratz, Robert A. Brodsky, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2013)

28 Background: Anticoagulants have been postulated to possess antitumor activity, although clinical data supporting this claim are conflicting. We sought to examine the effect of therapeutic anticoagulation on OS in men with mCRPC receiving first-line docetaxel chemotherapy. Methods: We retrospectively reviewed the records of 247 consecutive mCRPC patients who received first-line docetaxel chemotherapy between 1/1/1998 and 1/1/2010. Information on anticoagulant use, type of anticoagulant administered, indication for anticoagulation, and duration of anticoagulation were captured. Univariate and multivariable Cox proportional hazards regression models were developed to investigate the effect of anticoagulant use on OS. Results: In all, 29/247 men (11.7%) received anticoagulation (LMW heparin: 17/247; warfarin: 12/247). The indication was DVT in 15/247, PE in 9/247, and both DVT and PE in 5/247 men. In univariate analysis, anticoagulant use was associated with improved OS (any anticoagulant, HR 0.61 [95%CI 0.40–0.94] P=0.024; LMW heparin, HR 0.58 [95%CI 0.34–0.99] P=0.048; warfarin, HR 0.82 [95%CI 0.55–1.28] P=0.23). Median OS was 20.9 mo (with any anticoagulant) versus 17.1 mo (with no anticoagulant). In multivariable analysis, anticoagulant use remained a significant predictor of OS after adjusting for other prognostic factors (Table). Conclusions: Anticoagulant use is an independent predictor of OS in men with mCRPC receiving docetaxel. This finding is surprising given that the occurrence of venous thrombosis might be expected to negatively influence OS. If validated, these data may provide the impetus to explore the antitumor potential of anticoagulants in prospective clinical trials. [Table: see text]
VEGF<sub>165</sub>, Bcl-2, p53, COX-2 and HER-family expression in patients with stage I<sub>B</sub>-III<sub>A</sub> completely resected non-small cell lung cancer (NSCLC) and correlation with clinical outcome
Authors: E. Timotheadou, S. Murray, H. Linardou, A. V. Vrettou, J. Skrickova, P. Kosmidis, D. V. Skarlos, D. Pectasides, G. Fountzilas
Journal: Journal of Clinical Oncology (2005)

7246 Background: Clinical management of NSCLC remains challenging. Despite complete surgical resection, the majority of patients relapse and die of disease progression. The identification of prognostic molecular markers that could define high-risk groups may allow for more patients to benefit from tailored adjuvant treatment. Objectives: To describe the prevalence of molecular parameters HER-1, 2, 3 and 4, VEGF165, Bcl-2, p53, and COX-2 in tumor samples from patients with operable stage IB-IIIA NSCLC treated in the adjuvant setting with chemotherapy, consisting of paclitaxel 175mg/m2 and carboplatin AUC 6 every 3 weeks for 6 cycles. To determine the correlation between the above mentioned parameters and clinical outcome, time to treatment failure (TTF) and overall survival. Patients-Methods: Paraffin embedded tumor biopsies from 59 patients (52 men and 7 women, median age 62 years) with IB-IIIA completely resected NSCLC were analyzed by immunohistochemistry (IHC) and RT-PCR for the expression of VEGF165 and COX-2 (IHC) and for Bcl-2, p53, VEGF165, HER-1, -2, -3 and -4 (RT-PCR). Positive immunostaining for VEGF165 was defined by the staining of 25% or more of the cellular membranes and COX-2 the staining of 10% or more of the cells. Results: Immunohistochemical and RT-PCR analyses were completed in all of the 59 patients tumor tissues. 24 (40.7%) were VEGF165 positive and 25 (42.4%) were COX-2 positive by IHC. Analysis of intratumoral mRNA expression identified 28 (47.5%) VEGF165, 30 (50.9%) p53 and 18 (30.5%) HER-1 positive. After a median follow-up of 48.3 months (95% C.I. 35.3–61.3) the median survival was 43.2 months (95% C.I. 14.0–72.5), and TTF was 19.9 months (95% C.I. 14.5–25.3), while the 3-year survival was 57%. Conclusions: The expression of VEGF165, p53, HER-1 and COX-2 were frequent in our study of NSCLC. Expression analysis of the remaining parameters by IHC and RT-PCR are ongoing. Multivariate analysis of all parameters with clinicopathological data and outcome will be presented. No significant financial relationships to disclose.
Alteration of ADCC-related genes as a novel predictor of efficacy of cetuximab (cet)-based chemotherapy in patients (pts) with metastatic colorectal cancer (mCRC) (JACCRO CC-05/06 AR).
Authors: Yu Sunakawa, Dongyun Yang, Shu Cao, Chris Roberts, Eva Wang, Miriana Moran, Stephanie H. Astrow, Debrah Thompson, Jack Hsiang, Wu Zhang, Akihito Tsuji, Takehiro Takahashi, Tadamichi Denda, Mitsugu Kochi, Ken Shimada, Masahiro Takeuchi, Masashi Fujii, Toshifusa Nakajima, Wataru Ichikawa, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2016)

589 Background: Cet exerts its therapeutic effects not only through EGFR-signal blockade but also through antibody-dependent cell-mediated cytotoxicity (ADCC), mainly driven by natural killer (NK) cells. NK cells play a key role by releasing granzyme B (GZMB) via perforin (PRF1)-formed pores, leading to tumor cell apoptosis. CD137 (TNFRSF9) is expressed on NK cells, which regulates activation and proliferation of T cells. We hypothesized that genetic alteration in NK cell-mediated ADCC may serve as a predictor of cet in mCRC pts. Methods: Genomic DNA and RNA were isolated from tumor tissues of 77 KRAS exon2 wild-type (wt) pts enrolled in 2 Japanese phase II trials of cet plus oxaliplatin-based chemotherapy as 1st-line therapy, FOLFOX (n= 28/57, UMIN000004197) and SOX (n= 49/67, UMIN000007022). We evaluated associations between functional polymorphisms and gene expression of TNFRSF9, GZMB, and PRF1, and clinical outcome using PCR-based direct sequencing and molecular profiling panel (HTG EdgeSeq Oncology Biomarker Panel) based on next generation sequencing. Recursive partitioning (RP) method was also used to explore the associations. Results: In the population with median age of 63 years and follow-up time of 31.4 months (m), response rate (RR), median progression-free survival (PFS), and overall survival (OS) were 73 %, 10.0 m, and 33.9 m, respectively. TNFRSF9 rs161826 (A &gt; G) was associated with PFS but not RR or OS in both univariate (any G vs A/A: 9.2 m vs 13.8 m, HR 1.75, P= 0.030) and multivariate analyses (P= 0.050). No association of rs161826 with gene expression was observed. PRF1 polymorphisms were not associated with outcome, while high PRF1 mRNA expression had association with shorter PFS (9.7 m vs 18.0 m, HR 2.60, P= 0.028), and it remained significant in multivariate analysis (P= 0.002). In RP analysis, PRF1 mRNA expression also showed significant association with PFS. Conclusions: TNFRSF9 rs161826 and PRF1 gene expression are significantly associated with PFS in pts with KRAS wt mCRC treated with cet-based chemotherapy. Gene expression and variation in NK cell-mediated ADCC may predict efficacy of cet (UMIN000010635). Clinical trial information: UMIN000010635.
The Myocyte Enhancer Factor 2C (MEF2C) Is a Direct Transcriptional Target of HOXA9 and Mediates Leukemia Survival in Human Mixed-Lineage Leukemias.
Authors: Jorg Faber, Andrei V. Krivstov, Matthew C. Stubbs, Marry van den Heuvel-Eibrink, Andrew L. Kung, Christian M. Zwaan, Scott A. Armstrong
Journal: Blood (2007)
Association of timing of palliative care consult on quality care outcomes at a community based hospital.
Authors: Parag Bharadwaj, Sriram Yennu, Karen M Helfen, Leo J DeLeon, Joe Kim, Kathie S Zimbro, Douglas M Thompson, Aaron D. Bleznak
Journal: Journal of Clinical Oncology (2015)

166 Background: Timing of palliative care (PC) consults in hospitalized patients can have an impact on outcomes. Aim: To study the impact of the timing of consults on length of stay (LOS) of PC patients in a community based hospital over a span of 1 year. Additional outcomes included mortality and readmission rates. Methods: We conducted a retrospective review of medical records of consecutive patients who were referred to PC during the time period (November 2012- October 2013). LOS of PC patients consulted within and after 48 hours of admission were analyzed. Based on the timing of consult, mortality ratio of the two patient groups were analyzed. In addition, we analyzed the 30, 60 and 90 day readmission rates pre and post PC consult. Results: The LOS of patients seen by PC within 48 hours (N = 353) of admission was 1.20 (variance from expected) versus after 48 hours (N = 187) of admission was 6.28 (variance from expected). The mean difference in LOS between the groups was 5.08 days. The mortality ratio of the two groups was 1.01 (within 48 hours) versus 1.10 (after 48 hours) (p = .131). In addition the decrease in the 30, 60 and 90 day readmission rate was 61.5%, 47% and 42.1% respectively. Conclusions: Early PC consults were associated with a decrease in LOS and readmission rates with no increase in mortality rate. Further studies are needed to validate these findings in the community setting.
Intention to treat analysis of neoadjuvant chemoradiation and liver transplantation for perihilar cholangiocarcinoma.
Authors: Benjamin Loveday, Jennifer J. Knox, Laura A. Dawson, Gary May, Ur Metser, Anthony M. Brade, Anne M. Horgan, Bernard Cummings, David Grant, Steven Gallinger, Paul David Greig, Carol-anne Moulton
Journal: Journal of Clinical Oncology (2016)

394 Background: Neoadjuvant chemoradiation and liver transplantation is an option for selected unresectable patients with early stage perihilar cholangiocarcinoma (pCCA). This study aimed to determine the dropout rate, morbidity and survival of patients who entered a modified tri-modality protocol at Princess Margaret Cancer Centre. Methods: All patients enrolled into the protocol (Jan 2009 – Aug 2015) were included in the analysis. Enrollment criteria: ≤ 65 years old with brush biopsy-proven, unresectable pCCA proximal to the cystic duct, &lt; 3.5 cm in diameter. Neoadjuvant protocol consisted of conformal radiation therapy (54-75 Gy, 1.5 Gy BID) concurrent with Capecitabine 800 mg/m 2 BID until radiation completion. Following surgical staging patients received maintenance chemotherapy (Cisplatin 25 mg/m 2 and Gemcitabine 1000 mg/m 2 , day 1 and 8 of 21 day cycle), until transplant or progression. Intention to treat analyses were performed on prospectively collected data to determine time to progression (TTP), dropout rate, overall survival (OS), and number of biliary procedures. Results: Seventeen patients were enrolled, with a median age of 53.9 (26.7-62.8) years, and tumour diameter of 2.7 (2.0-3.4) cm. Five patients had primary sclerosing cholangitis. Median follow up was 14 (6-41) months. The cohort required a median of 3 (0-8) biliary stents, and percutaneous transhepatic biliary drainage in 11/17. Median TTP was 6 (2-16) months. Protocol dropout occurred in 10/17 due to metastatic disease identified during chemoradiation (2), surgical staging (6), or maintenance chemotherapy (2). No dropouts were due to neoadjuvant toxicity. Four patients underwent transplantation (two living donor, two deceased donor), and three are on the transplant waiting list. Median survival from first consultation and start of chemoradiation was 18.2 and 17 months, respectively. Conclusions: Neoadjuvant chemoradiation and liver transplantation for unresectable early stage pCCA is feasible, although dropout during the protocol is high. Less than half of patients who began the treatment protocol remained eligible for transplantation due to cancer progression or upstaging after surgical staging.
Velcade®, Thalidomide, Dexamethasone (VTD) Induction Therapy Followed by Melphalan, Prednisone, Thalidomide (MPT) Maintenance as a First Line Treatment for the Patients (pts) with Multiple Myeloma (MM) Who Are Non-Transplant Candidates: Early Analysis from the Korean Multiple Myeloma Working Party.
Authors: HyeonSeok Eom, Yeo-Kyeoung Kim, Jooseop Chung, Kihyun Kim, HyoJeong Kim, JongYul Jin, Young-Rok Do, Sukjoong Oh, HoYoung Kim, Cheolwon Suh, Chu-Myong Seong, Chul Soo Kim, Dong Soon Lee, Jae Hoon Lee
Journal: Blood (2007)
inSIRT trial: Single-center phase II study of yttrium-90 radioactive resin microspheres in the treatment of liver-predominant metastatic colorectal adenocarcinoma after failure of first-line combination chemotherapy.
Authors: Tony R. Reid, Eric Roeland, Shakeela Dad, Kelly Anne Shimabukuro, Paul Timothy Fanta
Journal: Journal of Clinical Oncology (2012)

e14079 Background: Liver metastases develop in half of colorectal cancer (CRC) cases and once metastatic, ~90% die due to their consequences. We are evaluating the aggressive management of liver metastases through the incorporation of selective internal radiation therapy (SIRT) using Yttrium-90 (Y-90) radioactive microspheres after evidence of progressive disease following 1st-line FOLFOX ± bevacizumab. Optimal timing for microsphere treatment relative to chemotherapy is not clearly established. Methods: Subjects with predominant hepatic metastatic CRC despite 1st-line FOLFOX based therapy ± bevacizumab are eligible. Interventional radiology and nuclear medicine assess the liver lesions and the subject receives SIRT followed by 2 nd -line FOLFIRI 4-6 weeks after the final SIRT. Results: To date, 9 metastatic CRC subjects have been treated and 10 subjects enrolled (goal 30 subjects). One subject was withdrawn due to progressive lung metastases. 4 of 9 subjects (45%) achieved PFS at 6 mos and average TTP is 7 months(0.7-21.3 mos). Overall treatment has been well tolerated, except one possible study related SAE of liver failure. The OS endpoint has not been achieved. Conclusions: Historically, 2nd-line FOLFIRI has achieved a 2.5 mos median PFS. Our preliminary results of 9 subjects with metastatic CRC show a PFS up to 21.3 monthsand 45% PFS at 6 mos. These encouraging results demonstrate the utility of an innovative direct approach to metastatic CRC after failure of 1st-line combination chemotherapy. Based on our promising preliminary results, our aim is to enroll 30-35 metastatic CRC patients. [Table: see text]
Cardiovascular disease in adult survivors of childhood and adolescent cancer: A report from the Childhood Cancer Survivor Study (CCSS)
Authors: D. A. Mulrooney, M. Yeazel, P. Mitby, T. Kawashima, W. M. Leisenring, M. Stovall, D. M. Green, C. A. Sklar, L. L. Robison, A. C. Mertens
Journal: Journal of Clinical Oncology (2008)

9509 Background: Previous research has shown that cardiovascular disease contributes to significant morbidity and mortality among survivors of childhood and adolescent cancer. Few studies have reported risk factors in long-term survivors who are now adults. Methods: This analysis includes 14,358 five-yr cancer survivors of the CCSS diagnosed ≤ age 21, between 1970–1986, with one of eight childhood cancers [leukemia, CNS tumors, Hodgkin’s or non-Hodgkin’s lymphomas, renal tumors, neuroblastoma, soft- tissue sarcomas, or bone cancers]. Self-reported cardiac outcomes occurring at least 5-yrs post-dx are compared to a sibling control group (N=3899) and across treatment groups using Cox proportional hazards models to estimate relative risks (RR) adjusted for age, gender, race, sociodemographic factors, and smoking status. Results: Survivors (54% males) were on average 7.8 yrs (0–20) at diagnosis, and 27.5 yrs (8–51) at follow-up. Compared to siblings, survivors were more likely to report congestive heart failure (CHF) (RR 5.7 95% CI 3.4–9.6), myocardial infarction (MI) (RR 4.9 95% CI 2.3–10.4), atherosclerosis (RR 10.2 95% CI 3.7–28.3), pericardial (RR 6.3 95% CI 3.3–11.9) and valvular disease (RR 4.8 95% CI 3.0–7.6), and coronary angiography (RR 8.2 95% CI 4.2–16.1). Anthracycline exposure ≥ 250 mg/m2 increased the risk of reported CHF (RR 4.1 95% CI 3.0–5.6), pericardial (RR 1.9 95% CI 1.3–2.9) and valvular disease (RR 1.8 95% CI 1.3–2.5), and angiography (RR 2.6 95% CI 1.8–3.7) compared to unexposed survivors. Radiation (RT) to the heart also increased the risk of CHF (RR 2.0 95% CI 1.4–2.8), MI (RR 1.9 95% CI 1.1–3.2), atherosclerosis (RR 5.3 95% CI 2.5–11.0), pericardial (RR 2.2 95% CI 1.4–3.3) and valvular disease (RR 2.8 95% CI 1.9–4.0), and angiography (RR 2.2 95% CI 1.5–3.2) compared to those survivors without cardiac directed RT. Conclusion: The occurrence of premature cardiovascular diseases is substantial in this young adult population of cancer survivors. No significant financial relationships to disclose.
Clinical core biopsy of locally advanced breast cancer performed in the physician's office without image guidance: Expedited pathway to diagnosis.
Authors: F. Wong, L. A. Martin, G. K. Pansegrau, C. Sherriff, S. Singh-Carlson
Journal: Journal of Clinical Oncology (2011)

e11525 Background: Patients with a clinical presentation of locally advanced breast cancer (LABC) need expedited diagnosis so that management can be initiated promptly. Well coordinated rapid diagnostic centres with triple assessment capability are generally not available in British Columbia (BC), Canada. Waits for image guided biopsy delay referral for neo-adjuvant treatment. A pilot LABC out-patient clinic was established at the BC Cancer Agency-Fraser Valley Centre in 2009. Patients presenting with clinical findings suggestive of LABC could be immediately referred by the family physician or surgeon for medical oncology assessment, and were seen with a median wait time of 7 days. Those without tissue diagnosis were also seen by breast surgeons the same day. If deemed suitable, breast clinical core biopsies (CCB) were immediately obtained by the surgeon using a 10 gauge vacuum assisted core biopsy needle. Success of this procedure was defined as achieving diagnosis with pathological receptor status without a second biopsy procedure. Methods: Between March 1st 2009-November 30th 2010, twenty patients were referred to the LABC clinic with no tissue diagnosis and no known metastases. They were assessed by breast surgeons for possible expedited diagnosis. Clinical information was reviewed in detail regarding the success rate of CCB. Results: Twenty patients ranging in age 38 to 83 underwent the procedure, with no surgical complications. The described clinical tumour size was larger than the reported imaging size in 90% of cases. Overall, 16/20 biopsies were successful. Four patients required further image guided biopsies, resulting in a gap of 6 – 13 days (median-7 days) from consultation to diagnosis. All clinical presentations with skin changes resulted in successful biopsies. Conclusions: In the absence of a triple assessment diagnostic centre, CCB can result in rapid diagnosis in 80% of patients with LABC, reducing wait times for neo-adjuvant treatment. Success rate of this procedure was increased in the presence of clinical skin changes.
Using deep sequencing of formalin-fixed paraffin embedded (FFPE) rectal cancer biopsy tissue to analyze miRNA expression in patients with rectal cancer.
Authors: Zhenbin Chen, Harry Gao, Bing Mu, Jinhui Wang, Xiwei Wu, Hanjun Qin, Wenyan Li, Julio Garcia-Aguilar
Journal: Journal of Clinical Oncology (2012)

487 Background: miRNAs have been shown to be involved in tumor initiation, progression and metastasis in many cancers including colorectal cancer. However, miRNA profiling specifically in rectal cancer is not well characterized. Our objective was to generate a miRNA expression profile in locally advanced rectal cancer using formalin fixed paraffin embedded (FFPE) biopsy tissue collected from patients with locally advanced rectal cancer. Methods: We collected pre-treatment biopsy tissue and matched normal tissue from 40 rectal cancer patients treated with pre-operative chemoradiation (CRT) and total mesorectal excision (TME). We extracted 50-1000ng of total RNA from FFPE biopsies and optimized small RNA sample preparation for deep-sequencing. We then performed deep sequencing on biopsy and matched normal tissue and compared miRNA expression in biopsy and normal tissues using paired T-test and multiple testing (Q-bound &lt;0.05) to determine significant miRNA expression changes in rectal cancer. Results: 182 miRNAs were differentially expressed in tumor versus normal tissues (Q-bound &lt;0.05); 15 of these miRNAs showed a greater than 2-fold change in expression in tumor tissue; mir-18a, mir-135b, mir-503, mir-584, mir-106b, mir-224, mir-92a, mir-181d were up-regulated and mir-375, mir-378, mir-378c, mir-137, mir-378, mir-147b, mir-30a were down-regulated. miRNA mir-31 showed the highest up-regulation in tumor tissue (16-fold increase) while mir-215 expression decreased 8-fold in tumor compared to normal tissue. Tumor and normal tissues were completely separated by hierarchical cluster analysis based on their distinctive miRNA profiles. Conclusions: We optimized small RNA sample preparation for deep sequencing of miRNAs, an approach which may be useful for quantifying miRNA expression in tissues with limited starting material. We also identified a novel miRNA expression profile in rectal cancer that may be useful as a diagnostic biomarker of disease.