tbuckley/cabot-search huggingface dataset:
Translation of evidence into funding policy: An overview of guidelines from the Cancer Care Ontario's Program in Evidence-Based Care (PEBC).
Authors: R. Ramjeesingh, R. M. Meyer, M. C. Brouwers, C. M. Booth
Journal: Journal of Clinical Oncology (2011)

e16513 Background: PEBC develops clinical practice guidelines through synthesis of best evidence. Ontario’s universal health insurance program funds cancer therapies based on Ministry of Health and Long-Term Care (MOHLTC) decisions. We evaluated key evidence associated with PEBC recommendations for use of targeted therapies (TT) and MOHLTC drug-funding decisions. Methods: We identified PEBC TT guidelines published before June 1, 2010. Key evidence (KE) supporting recommendations was extracted, prioritized, and associated with funding decisions. When there was more than 1 citation of KE, the following hierarchy was used (i) type: evidence highlighted by authors>published article>abstract; and (ii) level: meta-analysis (MA) or phase 3 RCTs (P3)>phase II trials (P2)>largest sample size. Funding decisions were extracted from MOHLTC documents. Results: For 23 guidelines related to 17 TTs, we identified 43 treatment recommendations; 39 (91%) did and 4 (9%) did not endorse use of the TT. Key evidence cited included 35 MA/P3 (81%) and 8 P2 trials (19%); coming from published articles (40/43; 93%) and abstracts (3/43; 7%). Key evidence evaluated overall survival (OS) (18/43; 19%); another time-to-event endpoint (TTE) (14/43; 33%) or response rate (RR) (8/43; 19%). Funding decisions and KE are shown in the table. Conclusions: Funding was approved for 74% of PEBC recommendations. Factors trending to association with declined funding are key evidence from P2 trial and/or RR. Further evaluations are required to assess magnitude of benefit and pharmacoeconomics. Key evidence associated with MOHLTC funding decisions for 31 CCO PEBC recommendations endorsing targeted therapy (TT).* Trial design Outcome** Publication status MA/P3 P2 OS+ TTE+ RR+ Article Abstract Recommendations associated with approved funding (n=23) 20 (87%) 3 (13%) 13 (57%) 8 (35%) 2 (8%) 22 (96%) 1 (4%) Recommendations associated with declined funding (n=8) 6 (75%) 2 (25%) 3 (38%) 4 (50%) 1 (12%) 6 (75%) 2 (25%) * Data for 31 cases reviewed by MOHLTC; 8 remain under review. ** One outcome is shown for each recommendation. In the absence of improved OS, recommendations are classified as having improved TTE or RR.
Association of mucin production and survival in colon cancer.
Authors: John Hogan, Georges Samaha, John Burke, David Waldron, Eoin Condon, John Calvin Coffey
Journal: Journal of Clinical Oncology (2013)

512 Background: Debate persists regarding the relationship between mucin production and cancer-related outcome following curative resection for colon cancer. Lack of consensus is due to (amongst other factors) discrepancies in definition, small cohort studies and the integration of both colon and rectal cancers. This study characterizes the relationship between mucin production and cancer-related outcome in an homogenous single-institute based cohort. Methods: A database spanning demographics, clinico-pathologic characteristics and prognostic factors was generated for all patients undergoing curative-intent colonic resection in the interval 2000 to 2010. Patients were categorized simply as mucin producing (i.e. MC) or non-mucin producing adenocarcinoma (NMC). Primary outcomes included overall survival (time to death from any cause) and disease free survival (time to loco-regional and systemic recurrence). Trends were established for MC and NMC using Kaplan-Meier estimates, plotted and compared using log-rank analysis. Findings significant on univariate analysis were incorporated into multivariate analysis. Cox proportional hazards model was employed to determine the associated hazard of both death and disease recurrence in each group. Statistical analysis was performed using R version 2.15. P &lt; 0.05 was considered significant. Results: 77 mucinous carcinomas (MC) and 358 non mucinous carcinomas (NMC) were included. On univariate analysis, MC was associated with improved overall survival (OS) (P=0.007). Both N1 (HR 1.625, P=0.011) and N2 (HR 2.7, P&lt;0.001) status were associated with adverse OS. On multivariate analysis, MC approached but did not reach statistical significance for improved OS (HR 0.543, P=0.061). A comparison of Kaplan-Meier estimates for overall survival in MC and NMC groups indicated that OS was significantly improved in the MC cohort (P=0.011). There was no difference in disease free survival (P=0.224). Systemic recurrence was greater in the NMC group (P=0.042). Conclusions: Mucin production in colonic adenocarcinoma appears associated with improved overall but not disease-free survival. In addition, the absence of mucin was associated with adverse systemic but not local recurrence.
Concomitant chemoradiation or RT/cetuximab versus induction TPF followed by chemoradiation or RT/cetuximab in locally advanced head and neck squamous cell carcinoma: A randomized phase III factorial study.
Authors: A. Paccagnella, M. G. Ghi, I. Floriani, A. Gava, A. Buffoli
Journal: Journal of Clinical Oncology (2011)

TPS196 Background: Concomitant chemoradiation (CRT) is the standard treatment for locally advanced squamous cell carcinoma (LASCC). RT plus cetuximab is superior to RT alone and it is an alternative treatment to CRT (Bonner, NEJM 2006). The efficacy of induction chemotherapy when added to standard treatment has never been demonstrated, however, induction cisplatin/fluorouracil [PF] plus docetaxel combination (TPF) is superior to PF when added to CRT or RT alone (Posner, NEJM 2005; Vermorken, NEJM 2005). Methods: This ongoing factorial phase III study is the implementation of a previous phase II randomized trial evaluating the efficacy of CRT with or without induction TPF. At the end of the phase II study a Monitoring Committee decided to continue the study as a phase III, as initially planned, based on the efficacy and safety data of the phase II study. This phase III four arm factorial study has now randomized 352 patients (target 420) with LASCC unresectable stage III-IVM0 of oral cavity, oropharynx, hypopharynx, age > 18 years, ECOG PS 0-1, measurable disease by RECIST, adequate organ function. One step randomization is adopted to assign patients to concomitant treatment alone CRT (arm A1) or RT/cetuximab (arm A2) or to 3 cycles of induction TPF followed by CRT (arm B1) or RT/cetuximab (arm B2). Two concomitant PF cycles are administered in the CRT arm. Primary endpoints are the comparison of 3-year overall survival (OS) between induction vs no induction and the incidence of G3-4 in-field toxicity between CRT and RT/cetuximab. During the planned ad-interim analysis, the Independent Data and Safety Monitoring Committee decided to increase the sample size from the initially planned 350 patients to 420 to detect an absolute difference of 12% in 3 years OS in favour of the induction arm. Assuming an hazard ratio of 0.675 this study will have 80% statistical power with a two-sided type I error of 0.05. The total number of 420 patients will also be able to detect a difference of 10%, in grade 3-4 in-field toxicity between CRT vs RT/cetuximab with a power of 80%.
DOCK180 Is Induced with Differentiation from CD14 Positive Monocytes and It Regulates Phagocytosis in Both Macrophages and Dendritic Cells.
Authors: Katsuya Fujimoto, Mitsufumi Nishio, Hiroshi Nishihara, Ikumi Sato, Lei Wang, Shinya Tanaka, Takao Koike
Journal: Blood (2005)
Urinary-activated HGF as a noninvasive biomarker for the diagnosis of prostate cancer.
Authors: C. R. Peng, A. J. Prager, E. Lita, M. H. Wernick, D. McNally, A. Kaushal, M. Sproull, K. Compton, W. L. Dahut, W. D. Figg, K. A. Camphausen
Journal: Journal of Clinical Oncology (2011)

e15144 Background: Hepatocyte growth factor or scatter factor has been linked to the proliferation, motility, and metastatic invasion of cancer cells. Pro-HGF, an inactive precursor, is cleaved into a biologically active heterodimeric form called activated HGF (AHGF). We evaluated the potential of AHGF as a diagnostic and prognostic urinary biomarker candidate for prostate cancer. Methods: Urinary levels of AHGF were determined via enzyme linked immunosorbent assay (Immuno-Biological Laboratories Co., Ltd, Japan) in duplicate. Samples were compared between men with localized (n=65) and metastatic (n=36) cancer and a healthy control group of men (n=19). AHGF concentrations were normalized with creatinine (Bayer DCA 2000+ Analyzer). Results: The difference of urinary AHGF levels between the control group (mean: 111.3 pg/mg, range: 27.0-250.0) and the prostate cancer groups (mean: 230.1 pg/mg, range: 20.9-1010.0) was statistically significant (p<0.0001). Furthermore, urinary AHGF concentrations were significantly different between the control and the localized group (mean: 235.2 pg/mg, range: 24.6-668.0) (p<0.0001) and between the control and the metastatic group (mean: 220.8 pg/mg, range: 20.9-1010.0) (p=0.0039). The area under the receiver operating characteristic curve associated with the diagnostic accuracy of HGF between control and prostate cancer groups was 0.75 (p=0.0006, 0.64 to 0.85 confidence interval). There was no significant difference between the localized and metastatic groups. Conclusions: Urinary levels of activated HGF have the potential as a novel noninvasive diagnostic marker for prostate cancer.
Comprehensive Quantitative Proteomic Profiling of the Pharmacodynamic Changes Induced By MLN4924 in Acute Myeloid Leukemia Cells Reveals Rational Targets for Combination Therapy
Authors: Valeria Visconte, Steffan T. Nawrocki, Kevin R. Kelly, Yingchun Han, Anthony Possemato, Sean Beausoleil, Aziz Nazha, Jaroslaw P. Maciejewski, Hetty E. Carraway, Anjali S. Advani, Mikkael A. Sekeres, Jennifer S. Carew
Journal: Blood (2015)
Significance of serum interleukin-6 in patients treated with radiotherapy for hepatocellular carcinoma.
Authors: Hyejung Cha, Eun Jung Lee, Jinsil Seong
Journal: Journal of Clinical Oncology (2015)

254 Background: Interleukin-6 (IL-6) is reported to contribute to aggressive tumor growth and resistance to treatment. In several cancers including esophagus, head and neck, and pancreas, high IL-6 is associated with poor treatment outcome after radiotherapy (RT). However, reports about significance of IL-6 in RT for HCC were rare. The aim of this study was to investigate the significance of serum IL-6 with treatment outcome in patients treated with RT for HCC. Methods: For patients treated with RT for HCC, blood samples were collected prospectively, before start and after completion of RT schedule. Serum IL-6 levels were measured with enzyme-linked immunosorbent assay kit. Patients’ clinical profiles were recorded. Results: Between September 2008 and October 2009, 51 patients were included in this study. Median follow-up duration was 12.3 months (range, 0.5-62.3). Baseline serum IL-6 level was 31.63 pg/ml and patients who had treatment history before RT showed higher baseline serum IL-6 levels than treatment (Tx)-naïve patients (53.09 vs. 15.35, p=0.028). Baseline IL-6 levels were higher in patients showing infield failure (59.70 vs. 14.96, p=0.022) and extrahepatic failure (40.50 vs. 17.88, p=0.072). In patients who had treatment history before RT, higher baseline IL-6 levels were associated with both infield and extrahepatic failure (p=0.014, p=0.032, respectively) in. However, this significance was not found in Tx-naïve patients. Higher baseline IL-6 levels were associated with short infield PFS (p&lt;0.0001) in entire patients and in patients who had treatment history before RT. After RT, serum IL-6 level decreased but it was not significant (29.54 pg/ml, p=0.794). And variation of serum IL-6 level was not associated with treatment failure. Conclusions: Baseline serum IL-6 levels seem significant in predicting treatment outcome in patients treated with RT for HCC. High baseline serum IL-6 levels were associated with infield and extrahepatic failure, especially in patients who had treatment history before RT.
Clinical significance of serum angiopoietin-like protein 2 in colorectal cancer patients.
Authors: Takahito Kitajima, Yuji Toiyama, Tadanobu Shimura, Shozo Ide, Hiroki Imaoka, Satoru Kondo, Mikio Kawamura, Yoshinaga Okugawa, Aya Kawamoto, Junichiro Hiro, Susumu Saigusa, Masaki Ohi, Koji Tanaka, Yasuhiro Inoue, Yasuhiko Mohri, Masato Kusunoki
Journal: Journal of Clinical Oncology (2014)

417 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted protein belonging to the angiopoietin family. It has been reported to act as a causative mediator of chronic inflammation and metabolic abnormalities. ANGPTL2 increases inflammatory carcinogenesis in several cancers, and its expression in tumor cells is highly correlated with the frequency of tumor cell metastasis through increased tumor angiogenesis and tumor cell epithelial-to-mesenchymal transitions. However, to our own knowledge, clinical significance of serum ANGPTL2 in cancer patients remains unknown. The aim of this study was to quantify serum ANGPTL2 level using ELISA, and to evaluate its clinical and prognostic significance in patients with colorectal cancer (CRC). Methods: We quantified serum ANGPTL2 levels from 194 CRC patients and normal 48 controls (NC) by ELISA. Next, we investigated ANGPTL2 expression in matched CRC tissues (n=194) by immunohistochemistry (IHC) to identify the source of circulating ANGPTL2. The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: Serum ANGPTL2 levels were significantly higher in CRC than in NC (p&lt;0.01) and gradually increased according to TNM stage progression. Serum ANGPTL2 levels discriminated CRC from NC with high accuracy (AUC=0.837). High serum ANGPTL2 was significantly associated with larger tumor size (p=0.03), undifferentiated adenocarcinoma (p=0.03), advanced T stage (p&lt;0.01), peritoneal metastasis (p&lt;0.01). In addition, Kaplan–Meier curves revealed that high serum ANGPTL2 were significantly associated with poor disease free survival (p=0.01) and overall survival (p=0.03). Interestingly, ANGPTL2 levels in serum from CRC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 expression in matched CRC tissues (r=0.14, p=0.03). Conclusions: Serum ANGPTL2, which might be derived from primary CRC tumor, has strong potential to serve as a noninvasive biomarker for CRC diagnosis and prognosis.
Feasability and reliabity of the assessment of BRAF and c-KIT mutations in cytologic samples from metastatic melanoma.
Authors: M. D. Lozano, T. Labiano, J. I. Echeveste, M. Montana, N. Gomez, M. F. Sanmamed, A. Gurpide, M. A. Idoate, S. Martin-Algarra
Journal: Journal of Clinical Oncology (2011)

8575 Background: Current advances in the understanding of melanoma biology and genetics gave a solid rationale to introduce different targeted therapies into clinical trials. In patients harbouring BRAF mutations, 60-80% objective response rate has been described after treatment with BRAF inhibitors like PLX4032 or GSK 2118436. Also, preliminary clinical experience in patients with mucosal or acral melanomas with gene amplification or activating mutations of c-KIT treated with imatinib, have shown high response rates and prolonged progression free survival. These results emphasise the importance of molecular information, even in those cases in which the diagnosis was made on small samples obtained through minimally invasive approaches. Cytology is an accurate and cost-effective tool for the diagnosis of metastatic cancer and in many times cytological smears are the only samples available from these patients. Methods: We studied BRAF and c-KIT mutations in cytological samples from 44 consecutive patients with metastatic melanoma. Diagnosis was made on fine needle aspiration in 34 cases, imprints in 6, direct eye touch in 1 and pleural and peritoneal fluid in 3. To assure tissue quality, DNA was extracted directly from Papanicolau stained smears on which cytological diagnosis was made. BRAF and c-KIT mutations were analysed by PCR and direct sequencing using an ABI PRISM TM 310XL. Results: Our series include 25 men and 19 women with a median age of 54 years. BRAF mutations was found in 22 patients (50%): V600E mutation in 19 (86,4%) and V600K in 3 (13,6%). c-KIT mutation was also studied in 18 patients and was found in 1 patient with acral melanoma (5.6%). BRAF status did not correlated with primary melanoma histology, disease free survival, brain metastases rate and overall survival. Conclusions: Activating mutations in BRAF are common in cutaneous melanoma (50% in our series). Mutational analysis of BRAF and c-KIT using cytological samples from patients with metastatic melanoma is feasible and it can be used to extend the benefits of targeted therapy to those patients from which biopsies are not available.
The relationship between systemic inflammation and postoperative outcomes following neoadjuvant chemoradiotherapy for rectal cancer.
Authors: Stephen Thomas McSorley, Bo Khor, Paul G. Horgan, Donald C McMillan
Journal: Journal of Clinical Oncology (2016)

682 Background: The magnitude of the systemic inflammatory response before and after surgery for rectal cancer is increasingly understood to have an impact on clinical outcomes. The aim of the present study was to examine the impact of neoadjuvant chemoradiotherapy (nCRT) on pre- and postoperative systemic inflammation and clinical outcomes in patients undergoing surgery for rectal cancer. Methods: Data was recorded prospectively for patients who underwent elective, potentially curative surgery for rectal cancer, from 2008 to 2015 at a single centre, n = 251. Patients had routine pre- and postoperative blood sampling. Results: Of the 251 patients, the majority were male (62%) and over 65 years old (57%) with node negative disease (66%). 85 patients (33%) were allocated to preoperative nCRT based on probable margin threatening disease at preoperative MRI. nCRT was significantly associated with a higher proportion of patients having neutrophil lymphocyte ratio (NLR) &gt; 5 (39% vs. 12%, p &lt; 0.001), and a modified Glasgow Prognostic Score (mGPS) of 2 (14% vs. 6%, p = 0.035) prior to surgery. There was no significant association between nCRT and the magnitude of the postoperative systemic inflammatory response or complications. Of the 85 patients who underwent nCRT, there was a small but significant reduction in CRP following treatment (3.25 mg/L vs. 4.1 mg/L, p = 0.007). Of the 16 patients who were systemically inflamed prior to nCRT, 9 patients achieved mGPS score 0 after treatment (p = 0.004). There was a significant association between having an mGPS score 1 or 2 both before and after nCRT and breaching established thresholds of CRP on postoperative days 2 (190mg/L, 86% vs. 33%, p = 0.002), 3 (170mg/L, 86% vs. 38%, p = 0.015) and 4 (145mg/L, 71% vs. 36%, p = 0.031). Conclusions: Allocation to nCRT was significantly associated with a systemic inflammatory response prior to surgery for rectal cancer. nCRT was significantly associated with attenuation of existing systemic inflammation. Such attenuation of the systemic inflammatory response may in part explain the efficacy of nCRT in patients with rectal cancer.
Prognostic role of β‐blocker selectivity and dosage regimens in heart failure patients. Insights from the <scp>MECKI</scp> score database
Authors: Stefania Paolillo, Massimo Mapelli, Alice Bonomi, Ugo Corrà, Massimo Piepoli, Fabrizio Veglia, Elisabetta Salvioni, Piero Gentile, Rocco Lagioia, Marco Metra, Giuseppe Limongelli, Gianfranco Sinagra, Gaia Cattadori, Angela B. Scardovi, Valentina Carubelli, Domenico Scrutino, Roberto Badagliacca, Rosa Raimondo, Michele Emdin, Damiano Magrì, Michele Correale, Gianfranco Parati, Sergio Caravita, Emanuele Spadafora, Federica Re, Mariantonietta Cicoira, Maria Frigerio, Maurizio Bussotti, Chiara Minà, Fabrizio Oliva, Elisa Battaia, Romualdo Belardinelli, Alessandro Mezzani, Luigi Pastormerlo, Andrea Di Lenarda, Claudio Passino, Susanna Sciomer, Annamaria Iorio, Elena Zambon, Marco Guazzi, Giuseppe Pacileo, Roberto Ricci, Mauro Contini, Anna Apostolo, Pietro Palermo, Francesco Clemenza, Giovanni Marchese, Simone Binno, Carlo Lombardi, Andrea Passantino, Pasquale Perrone Filardi, Piergiuseppe Agostoni
Journal: European Journal of Heart Failure (2017)
First-line dose-dense chemotherapy with docetaxel, cisplatin, folinic acid and 5- fluorouracil (DCF) plus panitumumab (P) in patients with locally advanced or metastatic cancer of the stomach or gastroesophageal junction (GEJ): A phase II multicenter trial.
Authors: Gianluca Tomasello, Wanda Liguigli, Laura Toppo, Rodolfo Mattioli, Federica Negri, Alessandra Curti, Margherita Ratti, Rossana Poli, Silvia Lazzarelli, Fabiana Gerevini, Chiara Colombi, Mario Martinotti, Massimo Rovatti, Lucio Olivetti, Rodolfo Passalacqua
Journal: Journal of Clinical Oncology (2015)

146 Background: Gastric cancer is a highly aggressive disease. No established standard first-line regimens are currently available. Aim of this study is to evaluate efficacy of dose-dense chemotherapy with DCF combined with P in patients (pts) with locally advanced or metastatic cancer of the stomach or GEJ. Methods: HER2 negative, ECOG PS 0-1, not previously treated pts, received up to 4 cycles of therapy with Panitumumab 6 mg/kg d 1, Docetaxel 60 mg/m2 d 1, Cisplatin 50 mg/m2 d 1, L-Folinic acid 100 mg/m2 d 1 and 2, followed by 5-FU 400 mg/m2 bolus d 1 and 2, and then 600 mg/m2 as a 22 h c.i. on d 1 and 2, every 2 weeks, plus Pegfilgrastim 6 mg on d 3. Pts aged ≥ 65 years were treated with the same chemotherapy schedule with a dose reduction by 30%. Pts with disease control after 4 cycles, received P until progression. Results: From 05/2010 to 01/2014, 52 consecutive pts were enrolled (75% M, 25% F; median age: 64.5 y, range: 42-75; metastatic 90%, locally advanced inoperable 10%; 96% adenocarcinoma; 13 pts with GEJ cancer). Primary end point was overall response rate (ORR). At 31 Aug 2014 cut-off date, 1 pt is still on treatment, 2 lost at f-up, 11 alive and 39 dead. 50 pts evaluable for response and all for toxicity. A median of 4 cycles (range 0-6) was administered. 3 CR, 29 PR, 10 SD and 8 PD were observed, for an ORR (by ITT) of 62% (95% CI, 48%-75) and a DCR of 81%. 26 pts entered the maintenance phase with only P and received a median 7.3 cycles (range 1-46). Median TTP was 4.8 months (95% CI, 4.1-6.9) and median OS was 9.4 months (95% CI, 7.4- 11.6). Most frequent grade 3-4 toxicities were: leucopenia (29%), neutropenia (19%), febrile neutropenia (13%), anemia (10%), asthenia (27%), mucosytis (13%), anorexia (17%), nausea/vomiting (12%), diarrhea (15%), ipokalemia (12%), and skin rash (25%). Two toxic deaths were registered (pulmonary aspergyllosis due to febrile neutropenia and gastric hemorrhage). Conclusions: Dose-dense chemotherapy combined with P is a very active regimen in gastric cancer. Due to a not negligible toxicity profile, it may represent a treatment option in neoadjuvant setting. Clinical trial information: 2009-016962-10.