tbuckley/cabot-search huggingface dataset:
Observational cohort study focused on treatment continuity of patients (pts) treated with XELOX plus bevacizumab (BV) for previously untreated metastatic colorectal cancer (mCRC).
Authors: Masahito Kotaka, Husao Ikeda, Taro Ikumoto, Masaki Tsuzie, Shinichi Yoshioka, Yoshihiko Nakamoto, Takaaki Ishii, Saori Goto, Atsushi Itami, Takeshi Kato
Journal: Journal of Clinical Oncology (2014)

661 Background: Systemic chemotherapy for unresectable mCRC has remarkably progressed as a results of wide spread use of irinotecan, oxaliplatin, anti-VEGF antibody and anti-EGFR antibody. It is important to continue treatment combined with these drugs and prolong progression-free survival so as to improve overall survival. Methods: We planned and conducted the prospective observational cohort study of 40 pts treated with XELOX + BV for previously untreated mCRC to investigate the treatment continuity of XELOX + BV. Endpoints were time to treatment-failure (TTF), overall response rate, resection rate, liver resection rate, progression-free survival (PFS), overall survival (OS) and safety. Eligibility criteria were (1) histologically confirmed mCRC, (2) with lesions evaluable by imaging, (3) previously untreated (except for surgery), (4) with condition enough to receive XELOX + BV, (5) written informed consent. Forty pts were planned to be enrolled during 2 years and followed up to 2 years. Results: Between July 2010 and June 2012, 40 pts were enrolled. Baseline characteristics were the following; male/female 24/16, median age 63 yrs (range 35-84 yrs), ECOG PS 0/1/2 33/6/1, primary cite colon/rectum 24/16, primary resection prior XELOX+BV yes/no 35/5, metastatic cite liver/lung/paraaorta/peritoneal/local recurrence/others 23/16/4/7/3/4, the number of metastatic cite 1/2/3 26/9/5.The median TTF was 5.3 months (95%CI: 3.6 – 9.1 months), and the reasons for treatment discontinuation were the following; CR 4 pts, resection 10 pts, progression 12 pts, adverse events 7 pts and pts refusal 3 pts. Four pts continued their treatments.The overall response rate was 52.5% (CR 6 pts and PR 15 pts), resection rate was 25.0% (liver 6 pts, lung 2 pts and primary 2 pts), and liver resection rate was 15.0%. The median PFS was 13.3 months (95%CI: 9.8 months – NR) and the median OS was not reached. Conclusions: Although the median TTF was 5.3 months, the median PFS was prolonged to 13.6 months. This might result from chemo-free interval caused by 4 pts’ CR and 9 pts’ resections. We will further investigate 40 pts’ 2-year survival data. Clinical trial information: UMIN000003416.
Serum Insulinlike Growth Factor Is Not Elevated in Patients with Early B-Cell Chronic Lymphocytic Leukemia but Is Still a Prognostic Factor for Disease-Progression.
Authors: Stefano Molica, Gaetano Vitelli, Rosanna Mirabelli, Giovanna Digiesu, Diana Giannarelli, Antonella Iorfida
Journal: Blood (2004)
Detection of circulating tumor cells in patients with advanced breast cancer according to the immunohistochemical subtype.
Authors: D. Peeters, P. van Dam, G. Van den Eynden, I. Benoy, S. J. Van Laere, P. A. van Dam, P. Huget, P. Pauwels, M. Peeters, P. B. Vermeulen, L. Y. Dirix
Journal: Journal of Clinical Oncology (2011)

e21022 Background: The enumeration of circulating tumor cells (CTC) with the EPCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (BC), and several studies suggest a similar role in patients with locally advanced tumors. However, BC has been shown to be a molecularly heterogeneous disease. The aim of this study was to assess potential differences in the detection of CTC according to the immunohistochemically defined molecular BC subtypes. Methods: We retrospectively analyzed CTC counts as performed by the CellSearch system in 7.5 ml blood of 100 patients with either primary lymph node positive (n=25) or metastatic BC prior to first line systemic treatment (n=75). Based on hormone receptor status, HER2/neu status and Bloom-Richardson histological grade of the corresponding primary tumor, patients were subdivided into 4 groups: patients with hormone receptor positive (HR+) low grade tumors (ER and/or PR+, grade I-II), HR+ high grade tumors (ER and/or PR+, grade III), HER2+ tumors (HER2 overexpression and/or FISH amplified) and triple negative (TN) tumors (ER, PR and HER2-). Results: CTC were detected in 5 of 25 (20%) patients with positive lymph nodes and 53 of 75 (70%) patients with distant metastases. In the total study population, the presence of as little as one CTC/7.5 ml blood was predictive for overall survival after a median follow up of 13.5 months (log-rank test: p=0.015). Significantly higher detection rates and numbers of CTC were observed in patients with HR+ low grade and TN tumors as compared to patients with HR+ high grade and HER2+ tumors (Kruskall-Walis test: p=0.002). Conclusions: Significant differences were observed in the detection of EPCAM positive CTC according to the immunohistochemical BC subtypes. Interestingly, CTC were detected more frequently in patients with HR+ low grade or TN tumors. However, larger patient series and longer follow up are required to assess whether these patients benefit most from prognostic CTC evaluation. HR+ low grade HR+ high grade HER2+ TN n=31 n=21 n=34 n=14 Median #CTC 7 0 1 3.5 Range #CTC 0-1687 0-253 0-115 0-886 ≥1 CTC/7.5 ml 21 (68%) 5 (24%) 21 (62%) 11 (79%) ≥5 CTC/7.5 ml 17 (55%) 3 (14%) 11 (32%) 6 (43%)
Phase I/II study of enzastaurin (ENZ) plus temozolomide (TMZ) and radiation therapy (XRT) in patients with glioblastoma multiforme (GBM) or gliosarcoma (GS)
Authors: N. A. Butowski, K. Lamborn, S. Chang, M. Page, J. Rabbitt, A. Fedoroff, R. Parvataneni, S. J. Nicol, D. Thornton, M. D. Prados
Journal: Journal of Clinical Oncology (2008)

3559 Background: ENZ, an oral serine/threonine kinase inhibitor, suppresses signaling through PKCβ and the PI3K/AKT pathways to induce apoptosis, reduce cell proliferation and suppress angiogenesis. PKCβ is activated by vascular endothelial growth factor, an angiogenic factor upregulated in most GBM. Phase I assessed the maximum tolerated dose of ENZ given concurrently with XRT plus TMZ and adjuvant with TMZ in patients (pts) with GBM or GS to define a phase II ENZ dose. Secondary objectives included safety, PK and pharmacodynamic (PD) parameters, response, quality of life (QOL), and utility of MR spectroscopy and perfusion imaging. Methods: Pts with newly diagnosed GBM/GS and KPS ≥60 were enrolled. Enzyme-inducing antiepileptic drugs were not permitted. Treatment started <5 weeks after diagnosis with XRT 60 Gy given over 6 weeks and TMZ 75 mg/m2 given daily during XRT and then at 200 mg/m2, from days 1–5 of a 28-day cycle. ENZ was given orally, once daily, during XRT at a starting dose of 250 mg/day (cohort 1). ENZ was escalated to 500 mg/day (cohort 2), if, during XRT and the first adjuvant cycle of TMZ, no more than 1/6 pts had a dose limiting toxicity DLT. DLTs included ≥G3 thrombocytopenia (Tp), G4 anemia/neutropenia, or ≥G3 nonhematologic toxicity. Planned treatment duration was 1 year. Phase II objectives are overall survival, progression-free survival, safety, PK/PD. and pharmacogenomics. Results: From 9/06–6/07, 12 pts enrolled in Phase I. There were no DLTs in the six pts of cohort 1. One pt withdrew and later progressed. As of 12/4/07, 5 pts in cohort 1 continue on ENZ 250 mg/day at ≥13 cycles. In cohort 2, 2/6 pts experienced a DLT; one G4 and one G3 Tp. One pt recovered to ≤G1 in <28 days and reinitiated adjuvant TMZ and ENZ with dose reductions. The other pt recovered to ≤G1 after 28 days, but discontinued. Three pts discontinued due to progressive disease and one pt continues on ENZ 500 mg/day. Phase II began accrual in 9/07. Conclusions: The combination of ENZ + XRT + TMZ in this study was well tolerated and the recommended dose of ENZ for proceeding to Phase II is 250 mg/day. Available Phase II results will also be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company
Efficacy and toxicity of q 2 weeks versus weekly versus q 3 weeks docetaxel in metastatic castration-resistant prostate cancer (CRPC).
Authors: Akshiv Malhotra, Bernard J. Poiesz
Journal: Journal of Clinical Oncology (2013)

206 Background: Standard treatment for metastatic CRPC is docetaxel 75 mg/m 2 q3weeks. Methods: We retrospectively studied patients treated with q 1, 2, or 3 weeks docetaxel regimens at 30, 60 and 75 mg/m 2 , respectively. The choice of regimen and duration of treatment was decided by their oncologist. Patients who had been in a clinical trial previously, or treated with any other chemotherapy before docetaxel were excluded. On this basis 41 patients were studied. Prostate specific antigen (PSA) was used as the primary method to assess response and progression. Response was a decline of &gt;/=50% from baseline value with no clinical or radiographic evidence of disease progression. For patients whose PSA did not decrease, progression was a &gt;/= 25% increase from baseline. If the PSA decreased without reaching response criteria, progression was a &gt;/= 25% increase from nadir. In those who responded, progression was a &gt;/= 50% increase from nadir. The increase had to be at least 5ng/ml. Toxicity was graded on the basis of CTCAE version 4.0. Response rate and toxicity in the 3 arms was compared using a two by two square t-test. Results: There were 12, 14, and 15 patients in the q1w, q2w and q3w arms, respectively. Response rates, mean progression free survival (PFS), median PFS, mean overall survival (OS), median OS, mean cumulative dose (MCD) and toxicity are shown in the Table. Three-year OS was 0%, 20%, and 0% in the q1w, q2w, and q3w arms, respectively. Toxicity was similar in the q1w, q2w, and q3w arms, except grade 1/2 neuropathy was higher in the q2w arm vs. the q1w arm (p=0.005). Conclusions: The MCD, response rates, PFS and OS in the q1w and q3w arms were similar to previously published reports. Patients in the q2w arm received a statistically significant higher MCD. Our data suggest a better outcome in the q2w arm as compared to the q1w and q3w arms. However, given the small number of patients studied, the results are not statistically significant. Toxicity was similar save for grade 1/2 neuropathy. [Table: see text]
Treatment (tx) intensity for patient groups by predefined tx aims and clinical characteristics in the management of patients (pts) with metastatic colorectal cancer (MCRC): Findings from a population-based survey in Germany
Authors: D. Arnold, L. Kellermann, H. Kröning, C. Goerg, D. Buschmann, H. Schmoll
Journal: Journal of Clinical Oncology (2011)

e14047 Background: According to the German S3 guidelines (Schmiegel et al., 2008), groups (gr) for suggested tx intensity are defined as based on an outcome-oriented algorithm (Schmoll & Sargent, Lancet 2007): Gr 1: pts with resectable liver mets (CLM), Gr 2: pts with CLM, potentially resectable after conversion tx, Gr 3a/b: pts with incurable disease, with disease related symptoms or at risk for rapid deterioration (3a) or without latter conditions (3b), gr 4: elderly or frail patients. In gr 2 and 3a, intense tx regimes (IT), by triple chemo or with targeted agents (TA), are recommended, whereas in 3b and 4, sequential tx starting with single agent or doublet tx are regarded as an option. Methods: A representative sample of 82 sites was selected with regard to the distribution of treated prevalence in institutions. Pts. characteristics as well as treating physicians suggestion for group distribution (according to guidelines), and tx characteristics were evaluated. Results: Data include 636 pts with first-line tx (Q4 '09): Distribution per gr is: 26% gr 1 (immediate surgery); in pts with upfront systemic tx: 16% gr 2, 12% gr 3a, 20% gr 3b, and 26% gr 4. Pts. in gr 2 were significantly (all <0.05) younger, had better performance status (PS), lack of comorbidity, had tx decision in non-university institutions and kras testing, but no more TA or IT. By contrast to the intention, IT and TA were given without statist. diff. in all gr., with the highest number (69% and 64%) in symptomatic pts (gr 3a). In a multivariate cluster analysis, 3 clusters overall including 89% of pts were determined (all p<0,05). In the only cluster with significantly higher use of TA, pts were younger (<70 y.), in better PS (≥80% KI), and asymptomatic (independent whether from tumor or lack of comorbidity). Conclusions: In clinical practice, the use of the complex, outcome-orientated determination system is not generally accepted. The decision making on tx intensity is rather based on pts characteristics and institutional factors. This underlines the need for development of further models.
Prediction of gastric cancer survival after gastrectomy using nomogram from 10,621 patients: Developed and validated using international databases.
Authors: Yanghee Woo, Woo Jin Hyung, Ki Jun Song, Yanfeng Hu, Naoki Okumura, Gyu Seok Cho, Sung Hoon Noh
Journal: Journal of Clinical Oncology (2013)

66 Background: Patient-specific prognosis for gastric cancer is difficult to determine. Internationally accepted AJCC TNM staging system currently provides the best framework for predicting a patient’s prognosis. However, a major weakness of the TNM system is that significant survival differences exist even within its subgroups. The objective of this study was to create a simple tool to accurately predict patient survival from gastric cancer after gastrectomy. Methods: Between December 1986 to March 2007, 10,621 patients were surgically treated for gastric cancer at a single institution and observed until death. A nomogram was determined using Cox proportional hazard regression for multivariate analysis and the Kaplan-Meier method for estimation of 5-year overall survival. Overall survival was the endpoint. The predicted probability of the nomogram for actual overall survival was compared to the 7 th edition AJCC TNM staging system. Then, the nomogram was validated using external data sets from four different institutions from Korea, Japan, and China. The number of patients in each data set was 1573 (A), 297 (B), 78 (C) and 767 patients (D). Results: Variables selected for the prediction model included age, gender, depth of invasion, number of metastatic lymph nodes (LN), total number of LN retrieved, and the presence of distant metastasis. The newly developed nomogram more accurately predicted a gastric cancer patient’s overall 5-year survival than the 7 th Edition AJCC TNM system (p=0.0024) with area under the curve 0.8023 (our nomogram) and 0.7869 (AJCC TNM staging system). The concordance indexes of the different validation sets were 0.824 (A), 0.835 (B), 0.916 (C), and 0.767 (D). Conclusions: Our simple nomogram requires minimal patient and tumor information. It accurately predicts the 5-year overall survival for a patient with gastric cancer after surgical resection. Already internationally validated with data sets of various sample sizes and from different countries, our new nomogram provides a useful tool for prognostication after gastrectomy with wide applicability in different patient populations and institutions.
A multicenter, open, randomized, phase II study to investigate the sequential administration of docetaxel and intermittent erlotinib versus erlotinib as a second-line therapy for advanced non-small cell lung cancer (NSCLC).
Authors: F. Aparisi, J. Garcia Sanchez, A. Sanchez-Hernandez, V. Giner, J. Muñoz-Langa, G. Esquerdo, A. López Jiménez, J. Garde, O. Juan Vidal
Journal: Journal of Clinical Oncology (2011)

e18036 Background: Patients (p) with advanced NSCLC have few treatment options after progressing to 1st-line platinum doublet chemotherapy (PDC). Several preclinical and phase I studies have suggested that sequential administration of erlotinib (E) and docetaxel could avoid possible negative interactions and optimize the benefit obtained against NSCLC. This randomized phase II was designed to address the clinical benefit obtained with the use of sequential administration of docetaxel and intermittent E. Methods: 70 p with advanced NSCLC progressing to previous PDC for advanced disease were randomized (1:1): Group A (n = 34): Docetaxel 75 mg/m2 day 1 and intermittent E (day 2-16), up to 4 cycles, followed by E in monotherapy Group B (n = 36): E in monotherapy. Treatment was administered until unacceptable toxicity or progression. Primary endpoint: rate of p free of progression at 6 months; secondary endpoints: progression-free survival (PFS), overall survival (OS), disease control rate (DCR), safety. The study has completed enrolment. Data from 32 p included are shown: 15 in Group A/17 in Group B. Results: Baseline characteristics: non-adenocarcinoma (71%), current/former smokers (93.7%), male (90.6%) and stage IV (83.9%). 6 months PFS: 14.3% in the sequential arm. PFS: 2.3 months (m) in Group A (95% CI 1.9 – 3.1) and 3.1 m in Group B (95% CI 2.0 – 4.5). Median OS: 4.9 m (95% CI 2.7 - -) in group A, slightly different than in Group B (6.0 m; 95% CI 2.5 – 6.0). DCR: 25% in the experimental group (95% CI 0.5 – 49.5) whereas in the E one was 50% (95% CI 23.8 – 76.2). Adverse events (AEs), including skin rash and diarrhea, were all generally tolerable. Although the incidence of treatment-related AEs was higher in Group A than in B, AEs leading to dose reduction were more common in the E arm (11.8% vs. 6.7%). Conclusions: Although this preliminary analysis shows no impact in the PFS and OS of this sequential treatment, data from 6 months PFS of the sequential arm may suggest a potential benefit of the combination. Final data of the primary endpoint from the whole population will be presented during the meeting.
The Molecular Pathway of Lysosomal Antigen Processing in Peripheral Blood Dendritic Cells (DC) Significantly Differs from That in Monocyte-Derived DC Generated Ex Vivo.
Authors: Christoph Driessen, Alexander Beck, Ekkehard Weber, Hans U. Haering, Hubert Kalbacher, Michael Reich, Herman Overkleeft, Eva Tolosa, Timo Burster
Journal: Blood (2004)
Preoperative chemotherapy in patients undergoing resection of colorectal liver metastases: Assessment of pattern of tumor response using CT registration imaging.
Authors: G. Cai, M. G. van Vledder, I. R. Kamel, L. A. Diaz, E. Boctor, T. M. Pawlik, M. A. Choti
Journal: Journal of Clinical Oncology (2011)

252 Background: A significant radiologic response from preoperative chemotherapy may successfully convert some unresectable colorectal liver metastases (CRLM) to resectable disease. Understanding the pattern of tumor shrinkage in relation to the hepatic structures such as the liver capsule and vascular pedicles is important. We sought to determine the spatial relationship between individual liver metastases before and after chemotherapy, as well as to adjacent intrahepatic structures. Methods: Using nonrigid registration of temporally separated CT scans before and after preoperative chemotherapy, 42 CRLM were evaluated in 27 patients with radiologic partial response. The response pattern was determined by independent observers and scored as: (1) asymmetric toward the liver periphery, (2) asymmetric toward the liver center, and (3) symmetric response. In addition, the shrinking pattern was characterized in relation to the liver capsule and major vascular pedicles, as well as clinicopathologic features. Results: Among the tumors evaluated, 38/42 lesions (90%) responded asymmetrically, with only 10% undergoing a symmetric contraction. 43% shrank toward the periphery and 47% centrally. Tumors in proximity to the liver capsule were more likely to respond peripherally compared to deeper lesions (p=0.013). Unexpectedly, R1 resection was more common in tumors with peripherally directed response vs. those with central or symmetric response (p=0.027). In addition, tumors within 5 mm of a single major vascular pedicle were more likely to shrink toward (59%) and not away from the vessel. No difference in response pattern was observed in relation to tumor size, chemotherapy regimen, or presence of steatosis. Conclusions: Tumors were found to respond asymmetrically in the vast majority of cases, either toward or away from the liver center. In addition, tumors in proximity to major vascular pedicles less commonly move away from these structures. These findings may have important implications when planning curative-intent resection or anticipating the ability to convert patients to resectable disease using preoperative chemotherapy. No significant financial relationships to disclose.
Primary results, NRG Oncology/NSABP B-35: A clinical trial of anastrozole (A) versus tamoxifen (tam) in postmenopausal patients with DCIS undergoing lumpectomy plus radiotherapy.
Authors: Richard G. Margolese, Reena S. Cecchini, Thomas B. Julian, Patricia A. Ganz, Joseph P. Costantino, Laura Vallow, Kathy S. Albain, Pat W. Whitworth, Mary E. Cianfrocca, Adam Brufsky, Howard M. Gross, Gamini S. Soori, Judith O. Hopkins, Louis Fehrenbacher, Keren Sturtz, Timothy F. Wozniak, Thomas E. Seay, Eleftherios P. Mamounas, Norman Wolmark
Journal: Journal of Clinical Oncology (2015)

LBA500 Background: The primary endpoint of NSABP B-35, a phase III trial comparing 1 mg/day anastrozole to 20 mg/day tamoxifen, each given for 5 years, was breast cancer-free interval (BCFI), defined as the time from randomization to any breast cancer (BC) event including local, regional, or distant recurrence or contralateral disease, invasive or DCIS. Methods: Postmenopausal women with ER-receptor or PgR-receptor positive (by IHC analysis) DCIS and no invasive BC who had undergone a lumpectomy with clear resection margins were randomly assigned to receive either 20 mg/day tam or 1 mg/day A (blinded) for 5 years. Stratification was by age (&lt;60 v ≥60). Results: From 1/6/2003 to 6/15/2006, 3,104 pts were entered and randomized (1552 in groups tam and A each). As of 2/28/15, follow-up information was available on 3,083 pts for OS and on 3,077 pts for all other disease-free endpoints, with mean time of follow-up of 8.6 years. There were 198 BCFI events, 114 in the tam group and 84 in the A group (HR, 0.73; p=0.03). 10-year point estimates for BCFI were 89.2% for tam and 93.5% for A. A significant time-by-treatment interaction (p=0.02) indicated that the effect was not evident until later in the study. There was a significant interaction between treatment and age group (p=0.04); benefit of A is only in women &lt;60 years old. As to secondary endpoints, there were 495 DFS events, 260 in the tam group and 235 in the A group (HR, 0.89; p=0.21). 10-year point estimates for DFS were 77.9% for tam and 82.7% for A. There were 186 deaths, 88 in the tam group and 98 in the A group (HR, 1.11; p=0.48). 10-year point estimates for OS were 92.1% for tam, 92.5% for A. There were 8 deaths due to breast cancer in the tam group and 5 in the A group. There were 63 cases of invasive breast cancer in the tam group and 39 in the A group (HR, 0.61; p=0.02). There was a non-significant trend for a reduction in breast second primary cancers with A (HR, 0.68; p=0.07). Conclusions: Anastrozole provided a significant improvement compared to tamoxifen for BCFI, which was seen later in the study, primarily in women &lt;60 years. Support: CA12027, 37377, 69651, 69974; 180868, 180822, 189867 196067, 114732; AstraZeneca Pharmaceuticals LP. Clinical trial information: NCT00053898.