tbuckley/cabot-search huggingface dataset:
Long-term survivorship in pancreatic adenocarcinoma.
Authors: M. A. Gubens, P. L. Kunz, G. A. Fisher, J. M. Ford, D. Lichtensztajn, C. A. Clarke
Journal: Journal of Clinical Oncology (2011)

175 Background: Pancreatic cancer is one of the most lethal malignancies, with an estimated 5-year survival rate of 6%, often due to advanced stage at diagnosis. However, there is a small population of patients, even with metastatic disease, who survive 3 years and beyond. Methods: Cases of pancreatic adenocarcinoma diagnosed from 1998 to 2005 were identified in the California Cancer Registry. A multivariate logistic regression model was constructed to predict the outcome of 3+ year survival according to demographic, disease and treatment variables defined a priori: age, gender, race/ethnicity, socioeconomic status (SES), histology, stage, treatment within 4 months of diagnosis (surgery, chemotherapy, and/or radiation), prior cancer history, and treatment at an academic hospital. Results: Among 54,475 cases of pancreatic cancer with ≥3 years of follow-up data available, median survival was 3.5 months. 2,855 patients (5.2%) survived at least 3 years, of whom 19% had remote stage disease at diagnosis. On multivariate analysis, advanced age was associated with decreased odds of long-term survival (p&lt;0.01). By race, Asian/Pacific Islanders (odds ratio (OR) 1.76, p&lt;0.01), Hispanics (OR 1.29, p=0.01) and non-Hispanic blacks (OR 1.24, p=0.14) were more likely to be long-term survivors than non-Hispanic whites. There was a gradient toward increased long- term survival for patients with higher SES (OR 1.49 for highest vs. lowest quintile, p&lt;0.01). Mucinous tumors were associated with higher long-term survival than other adenocarcinomas (OR 2.21, p&lt;0.01). Localized (OR 6.82) and regional stage disease (OR 2.61) showed more long-term survival than remote stage disease, both p&lt;0.01. Surgery (OR 8.20, p&lt;0.01), chemotherapy (OR 1.44, p&lt;0.01), and radiation therapy (OR 1.25, p=0.02) increased the odds of long-term survival, as did treatment at an academic hospital (OR 1.54, p&lt;0.01). Conclusions: In a well- characterized population-based registry with rigorous follow-up, we were able to identify a cohort of long-term survivors of pancreatic adenocarcinoma as well as factors associated with their exceptional survival. Planned future work with this cohort includes case-control studies making use of tumor and germline specimens, as well as survivorship research. No significant financial relationships to disclose.
A retrospective study of first-line combination chemotherapy in advanced colorectal cancer: A Korean single-center experience.
Authors: S. Lee, J. Park, S. Park, W. Kang, H. Lim, Y. Park, K. Park, J. Lee
Journal: Journal of Clinical Oncology (2011)

623 Background: Fluoropyrimidine-based combination chemotherapy, in combination with either oxaliplatin or irinotecan, have demonstrated efficacy and tolerability against advanced colorectal cancer (ACC). Methods: Between Jan 2006 and Dec 2007, 478 ACC patients were treated with combination chemotherapy in first-line setting: 5-fluorouracil, folinic acid plus oxaliplatin (FOLFOX, n=172), 5-fluorouracil, folinic acid plus irinotecan (FOLFIRI, n=95), capecitabine plus oxaliplatin (XELOX, n=155), and capecitabine plus irinotecan (XELIRI, n=56). FOLFOX and FOLFIRI were repeated every 2 weeks, whereas XELOX and XELIRI were repeated every 3 weeks until disease progression or unacceptable toxicity occurred or until a patient chose to discontinue treatment. Results: The median age was 58 years (range, 19-84 years) and the median chemotherapy duration for FOLFOX, FOLFIRI, XELOX and XELIRI were 4.9, 4.5, 5.7 and 5.4 months, respectively. Combination chemotherapy regimens were generally well tolerated. The estimated median PFS for all patients was 6.8 months (95% confidence interval, 6.3-7.3 months). No statistically significant difference in PFS was found each regimen used as first-line chemotherapy. Sixty-percent (n=290) of patients received second or further lines of therapy after failure. Conclusions: Fluoropyrimidine-based combination chemotherapy regimens appear to be equally active and tolerable as first-line therapy for ACC. No significant financial relationships to disclose.
Impaired coronary flow reserve in patients with metastatic cancer treated with sunitinib.
Authors: F. Sen, I. Yildiz, H. Oflaz, F. Oz, L. Kilic, A. Gurdal, M. Basaran, S. E. Bavbek
Journal: Journal of Clinical Oncology (2011)

e15136 Background: Hypertension is one of the major side effects of sunitinib, an angiogenesis inhibitor and used in the treatment of metastatic renal cell carcinomas (mRCC) and gastrointestinal stromal tumours (GIST). Endothelial dysfunction, an early and reversible event in pathogenesis of atherosclerosis, is suggested to be one of the possible underlying mechanisms of hypertension caused by angiogenesis inhibitors. Coronary flow reserve (CFR) measurement by trans-thoracic Doppler echocardiography (TTDE) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. We have used TTDE to evaluate endothelial function and coronary microvascular function in mRCC and GIST patients under sunitinib treatment. Methods: Eighteen metastatic cancer (16 mRCC and 2 GIST) patients on sunitinib treatment and twenty seven healthy subjects were enrolled in this cross-sectional study. TSH, lipid profile, creatinine, hemoglobin, glucose, C-reactive protein, anthropometric and physical parameters of patients were recorded. CFR recordings were performed by the Vivid 7 echocardiography device. Results: CFR was significantly lower in patients than that in controls (1.82±0.4 vs. 2.71±0.8; respectively, P < 0.001). An impaired CFR was found in 13 (72 %) patients whereas all controls had normal CFR values. CFR was inversely correlated with the duration of sunitinib treatment (r = -0.36, P = 0.01), hsCRP (r = -0.574, P = 0.01) and erthyrocyte sedimentation rate (r = -0.5, P = 0.02). Conclusions: Our findings indicate that CFR is significantly impaired in cancer patients on sunitinib treatment. TTDE may be a suitable noninvasive method to monitor early abnormalities of coronary arteries in patients who have improved survival due to sunitinib treatment.
Association between preoperative neutrophil-lymphocyte ratio (NLR) and clinical outcomes in patients with gastric cancer.
Authors: Akihiro Suzuki, Ryotaro Takano, Osamu Takahashi, Takashi Taketa, Yuhsuke Shimodaira, Kazuki Sudo, Hironori Shiozaki, Seiji Ohigashi, Hisashi Onodera
Journal: Journal of Clinical Oncology (2014)

29 Background: The neutrophil-lymphocyte ratio (NLR) is related to inflammatory status of patients with some cancers. We hypothesize that preoperative NLR is associated with clinical outcomes in patients with gastric adenocarcinoma. Methods: We identified 458 gastric cancer patients who had curative gastrectomy at our institute between 2000 and 2009. All patients had baseline staging including blood test, CT scan and an endoscopic biopsy. Multiple statistical methods were used to analyze clinical outcomes. Results: Most patients were men and most had stage I. The median follow-up time was 74.8 months (95% C.I; 69.5-80.2). The estimated overall survival (OS) and recurrence-free survival (RFS) rate at 5 years were 76.1 +/- 2.1% and 78.6 +/- 2.2%, respectively. We divided 2 groups by NLR that cut off point was 4. In the stage I patients, the median OS and RFS of high and low NLR patients were not different (p=0.63, p=0.92, respectively). However, in stage II, III and IV patients, RFS of those were significantly different (p=0.027). In multivariate analyses, age (p&lt;0.001) and baseline stage (p&lt;0.001) was an independent prognosis factor for OS, and high NLR (p=0.005) and baseline stage (p&lt;0.001) was an independent risk factor for RFS. High NLR had tendency to be associated with poor OS (p=0.069) in multivariate analysis. Conclusions: A high preoperative NLR may be a useful biomarker to predict a poor prognosis patient with gastric cancer before surgery.
The effect of E7080, a VEGFR and FGFR tyrosine kinase inhibitor (TKI), on BRAF wild-type melanoma.
Authors: Y. Funahashi, J. Matsui, Y. Minoshima, A. Yokoi, T. Abe, K. Okamoto, K. Takahashi, T. Kadowaki, G. Kuznetsov, S. Agoulink
Journal: Journal of Clinical Oncology (2011)

8566 Background:E7080 is a TKI targeting VEGFR1-3, FGFR1-4, KIT, RET and PDGFR. Anti-tumor activity has been observed in melanoma patients in phase I. This study examines the mode of action of E7080 in preclinical melanoma models Methods: Mutational status of 18 genes (9 RTKs, 7 oncogenes and 2 tumor suppressor genes) was determined in 14 human melanoma cell lines. Gene profile and biomarkers of anti-angiogenesis and anti-tumor activity of E7080 were investigated in vitro and in vivo by gene expression analysis in a melanoma cell line panel and in human melanoma tissues. Results: 18 types of mutation (mu) were found among 9 RTKs in ten of 14 melanoma cell lines. 2 mu of BRAF, 9 mu of TP53, 3 mu of PTEN, 2 mu of CDKN2a and 1 mu of NRAS were also found among 9, 9, 3, 2 and 1 melanoma of 14 cell lines, respectively. 4 of the 5 melanoma with BRAF wild type (wt) were the most sensitive to E7080 in mouse xenograft models, while 5 of the 6 with BRAFmu/PTENwt were the most resistant, suggesting 3 sub-groups for sensitivity to E7080 based on BRAF/PTEN status: 1; BRAFwt/PTENwt, 2; BRAFmu/PTENmu and 3; BRAFmu/PTENwt. % of pericyte-covered tumor vessels was 25%, 29% and 35% among 3 sub-groups, respectively. Anti-tumor activity of E7080 was correlated to % of pericyte coverage in groups 1 and 2, in which tumor vessels are sensitive to E7080. DNA microarray analysis demonstrated decreased FGFR1-4 expression in BRAFmu melanoma, while qPCR analysis showed that FGFR2 and FGFR3 expression were significantly higher in BRAFwt than BRAFmu in human melanoma tissues. E7080 inhibited in vitro proliferation of BRAFwt melanoma, which overexpressed FGFR3. Knockdown of FGFR3, FRS-2a, NRAS and AKT-3 genes with siRNA transfection inhibited proliferation of E7080-sensiteve melanoma. Conclusions: BRAF/PTEN mutation status was associated with pericyte coverage of tumor vessels and the expression of FGFR1-4 in a panel of melanoma cell lines. E7080 showed superior anti-tumor activity against BRAFwt melanoma, in which the type of tumor vessels was sensitive to angiogenesis inhibition by E7080 and a subgroup of which were dependent on FGFR3 signaling.
Association of topoisomerase II expression and cancer-specific death in patients with surgically resected clear cell renal cell carcinoma.
Authors: Faithlore Patrice Gardner, Richard Wayne Joseph, Daniel Serie, Tracy W. Hilton, Mansi Parasramka, Jeanette Eckel-Passow, John Cheville, Bradley C. Leibovich, Alexander S. Parker
Journal: Journal of Clinical Oncology (2013)

e15539 Background: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. Methods: We identified 1,380 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/16/1990 and 4/14/2009. TOP2a expression was assessed using IHC and scored as number of positive cells per mm 2 . We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features we employed Kruskal-Wallis tests and for associations with cancer-specific survival we generated Cox proportional hazard regression models. Results: HigherTOP2a expression is associated with later stage, higher grade and higher MayoSSIGN score (all p &lt; 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend &lt; 0.0001), and this association remained strong after after multivariate adjustment for well-known predictors of RCC aggressiveness. Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.62 95% CI 1.95-3.54; p&lt;0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ~95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.48 95% CI 1.56-7.76; p =0.002). Conclusions: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.
Using touch-based technology to screen patients in the ICU.
Authors: Finly Zachariah, Matthew J. Loscalzo, Rupinder Sidhu, David Horak, Sorin Buga
Journal: Journal of Clinical Oncology (2016)

76 Background: The intensive care unit (ICU) is associated with high mortality rates, significant costs, along with occasionally futile and non-indicated care. Surveys of patients indicate the majority wish to focus on comfort and being at home at the end of life as opposed to the aggressive interventions received in the hospital. Although a small percentage of patients may be awake, medical teams look to the families to provide the direction of care for a patient in the ICU. City of Hope National Medical Center has utilized tablet-based screening of caregivers for years, and now in conjunction with delirium screening has started to roll out tablet-based screening for patients who are awake and do not have delirium. Methods: In parallel with a task force working to assess and address delirium in the hospital, team members from the Department of Supportive Care Medicine and the ICU developed and tested a survey on a tablet-based screening platform. Awake patients are screened for delirium using the confusion assessment method (CAM-ICU). If patients are awake and have a “negative” CAM-ICU, they are provided a tablet to take a five question survey. The questions were written to the sixth grade language level, reviewed by the Patient and Family Advisory Council and non-ICU patients commented on comprehension and emotional response prior to implementation in the ICU. The questions covered topics including orientation, symptoms to be addressed and confidence level in communicating wishes and values. Results: We have successfully administered tablet-based screening for five patients in the ICU, including one on a ventilator with a tracheostomy. Responses are electronically sent to the medical team. By the time of the conference, we will have screened over 50 patients, including patients who are intubated. Conclusions: Assessment of patient wishes and values should be done far before a patient enters the ICU. Unfortunately this does not always occur. This tablet-based screening pilot was a test of concept for feasibility. Although not ideal, capturing a patient’s values and wishes in the ICU has the potential to further assure care plans are individualized, minimize unwanted treatment options and facilitate possible transitions and improved care.
FAFOXIRI: A phase II trial of an alternating regimen of irinotecan/5-fluoruracil/folinic acid and oxaliplatin/5-fluoruracil/folinic acid in metastatic colorectal cancer
Authors: V. D. Ferrari, F. Valcamonico, V. Amoroso, L. Vassalli, S. Grisanti, P. Marpicati, E. Simoncini, G. Rangoni, G. Marini
Journal: Journal of Clinical Oncology (2005)

3660 Background: To assess the feasibility and efficacy of a combination schedule of sequential irinotecan (CPT11), oxaliplatin (L-OHP), brief infusional fluoruracil (5-FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer (MCC) patients.Methods: From January 2001 to October 2004, 52 (male 62%) patients were enrolled: median ECOG performance status was 0 (range 0–2), the most common metastatic site was liver (65% of pts), median age was 65 years (range 35–79) and 45% of patients were >65 years. Primary tumour site was colon 87%. Schedule was: irinotecan 125 mg/m2 as a 90-minute intravenous (IV) infusion on day 1 and 8, followed by FA 20 mg/m2 as IV bolus, and 5-FU 500 mg/m2 over 2 hours IV infusion. L-OHP was administered on day 15 at 85 mg/m2 as a 90-minute infusion. Escalated doses of FA (60 mg/m2 IV bolus) and 5-FU (550–650 mg/m2 as a 2-hour IV infusion) were given on days 15–16. Treatment was repeated every 4 weeks. The median number of cycles currently is 6 (range 4–9) and to date 283 cycles are administered. Results: Data are available for 48 pts, in 4 pts therapy is ongoing. 23/48 valuable patients attained a complete (n=4) or partial (n=19) response, leading to an overall response rate of 48% (95% CI, 34% to 62%). Eighteen (37.5%) patients showed stable disease, with an overall disease control of 85%. The median time to tumor progression was 10.3 months (95%CI, 10 to 10.6 months), median follow-up was 16.4 months. All patients were assessable for toxicities. The major adverse events were grade 3 neutropenia (6%) and grade 3 nausea/vomiting (6%). Neither toxic death nor life-threatening febrile neutropenia were reported. Chemotherapy was never stopped for adverse events. Conclusions: This triplet combination is extremely well-tolerated, manageable and effective in term of tumor response and time to progression. Elderly patients benefit by this regimen, without suffering significant toxicity. No significant financial relationships to disclose.
Development of a molecular profiling assay for circulating tumor cells (CTCs) utilizing automated multiplexed in situ hybridization for metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Dea Nagy, Mateus Crespo, Gerhardt Attard, Susana Miranda, Karl Garsha, Ubaradka G. Sathyanarayana, Steve Yun, Michael Otter, Phillip Miller, Gary Pestano, Johann Sebastian De Bono, Ryan Dittamore
Journal: Journal of Clinical Oncology (2012)

39 Background: ERG gene rearrangements lead to overexpression of the ERG oncogene in 50% of localized and metastatic prostate cancers. Recent studies have indicated that this gene fusion correlates with androgen sensitivity in prostate cancer patients and an association with increased DNA Repair activity (PARP1). The PTEN tumor suppressor has also been shown to regulate the AKT pathway, and related to increased PARP1 activity. We hypothesized that future PARP1 inhibitors and other targeted therapies for mCRPC will likely require the development of a companion diagnostic assay for measuring ERG rearrangement and PTEN deletion status in CTCs. Methods: We isolated CTCs utilizing the CellSearch system from mCRPC patients for enumeration. Following enumeration, the cells were transferred to glass slides and interrogated utilizing the automated Benchmark staining platform with multiplexed Quantum Dot FISH inclusive of probes for 5’ERG, 3’ERG, PTEN, and Cen 10. FISH signals were visualized utilizing spectral imaging. Results: Successful transfer of the CTCs from the CellSearch to a glass slide were achieved In model cell line systems, in cultured cells (LnCaP and VCaP) either directly or after spiking to PBL and five out of 6 times we were able to successfully demonstrate simultaneous single copy 5’ and 3’ ERG and PTEN/Cen 10 labeled probes. Studies are in progress to extend the clinical utility of this assay to isolated CTC from cases with metastatic prostate cancer. Conclusions: CTCs are likely to be utilized clinically for monitoring disease progression mCRPC patients as measures for therapeutic efficacy. As more therapeutics are approved for use in mCRPC patients, the ability for oncologists to molecularly characterize the type of CTCs driving tumor burden is likely to play a significant role in optimizing patient management by determining the type and the sequence of future targeted therapies. We have for the first time demonstrated a platform to molecularly characterize patient CTCs on an automated platform that is amenable to standard clinical use.
Discontinuing VEGF-targeted therapy (VEGF-TT) for progression versus toxicity impacts outcomes of second-line therapies in metastatic renal cell carcinoma (mRCC).
Authors: Guillermo de Velasco, Wanling Xie, Frede Donskov, Laurence Albiges, Benoit Beuselinck, Sandhya Srinivas, Neeraj Agarwal, Jae-Lyun Lee, James Brugarolas, Lori Wood, Christian K. Kollmannsberger, Sun Young Rha, Scott A. North, Ravindran Kanesvaran, Brian I. Rini, Reuben James Broom, Haru Yamamoto, Marina Dusevic Kaymakcalan, Daniel Yick Chin Heng, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2016)

503 Background: A significant minority of mRCC patients prematurely discontinue first-line (1L) VEGF-TT due to toxicity. Whether clinical outcomes differ in patients receiving second line (2L) TT based on reason for discontinuation of 1L are unknown. Methods: Patients from 15 International mRCC Database Consortium (IMDC) centers who started 2L TT were included and the reason for discontinuation of 1L collected. Treatment outcomes of 2L, including response, time to treatment failure (TTF) and overall survival (OS) were assessed. Results: 1124 patients were identified: 866 patients (77%) discontinued 1L VEGF-TT due to progression, 208 patients (19%) due to toxicity. 50 patients (4%) who discontinue due to other reasons were excluded. The reason for discontinuation of 1L did not differ by IMDC risk group at start of 1L VEGF-TT (p=0.54) or 2L therapy (p=0.52). Median time from 1L VEGF-TT initiation to start of 2L in patients who progressed or stopped prematurely due to toxicity was 9.8 and 7.9 months, respectively. Compared to patients who stopped 1L VEGF-TT due to progression, patients who stopped due to toxicity had longer drug free interval between 1L and 2L (1.4 vs. 0.7 months; p&lt;0.001), greater clinical benefit (CR/PR/SD) in second line (68% vs. 56%; adjusted OR: 1.58 (95%CI:1.07,2.35), p=0.023) and longer OS (17.4 vs. 11.2 months; adjusted HR: 0.69 (0.56,0.84), p=0.0002) adjusted for type of therapy, time to initiation of 2L, IMDC risk group and number of metastases at 2L (Table). Conclusions: mRCC patients with VEGF TT discontinuation 1L due to toxicity have better outcomes with 2L therapy than patients who stop therapy because of progression. These findings should be taken in consideration when designing clinical trials for second-line therapies in mRCC. [Table: see text]