tbuckley/cabot-search huggingface dataset:
Detection of viable human circulating tumor cells using telomerase-specific GFP-expressing bioengineered adenovirus in patients with gastric cancer: A feasibility study.
Authors: T. Fujiwara, F. Uno, Y. Hashimoto, Y. Shirakawa, T. Nagasaka, S. Kagawa, Y. Urata
Journal: Journal of Clinical Oncology (2011)

18 Background: The presence of circulating tumor cells (CTC) in the peripheral blood is associated with short survival and, therefore, the detection of CTC is clinically useful as prognostic factors of disease outcome and/or surrogate markers of treatment response. Recent technical advances in immunocytometric analysis and quantitative real-time PCR have made possible to detect a few CTC in the blood; however, there is no sensitive assay for detecting viable CTC. We developed a new approach to visually detect live CTC among millions of peripheral blood leukocytes using telomerase-specific replication-selective adenovirus expressing green fluorescent protein (GFP). Methods: We constructed a GFP-expressing attenuated adenovirus, in which the telomerase promoter regulates viral replication (OBP-401, TelomeScan). The detection method for viable human CTC in the peripheral blood involves a three-step procedure including the lysis of red blood cells, the subsequent addition of OBP-401 to the cell pellets, and the automated scan under the fluorescent microscope. We analyzed fresh blood samples collected from 37 patients with histologically confirmed gastric cancer. We further assessed the CTC dynamics in patients who were undergoing chemotherapy or surgery to demonstrate the clinical potential of our approach for monitoring treatment responses. Results: OBP-401 increased the signal-to-background ratio as a tumor-specific probe, because the fluorescent signal can be amplified only in viable human tumor cells by viral replication. Although the CTC level varied widely, ranging from 0 to 47 in 5-ml samples, 26 gastric cancer patients (70.3%) had more than one CTC; there was, however, no apparent relationship between CTC counts and TNM stages. Patients who had a recurrence of gastric cancer had decreased CTC counts after systemic chemotherapy. In the patients who underwent surgery, the CTC level dropped after complete resection. Conclusions: This GFP-expressing virus-based method is simple and allows precise enumeration of CTC, which might be useful for monitoring the efficacy of local and systemic treatments. [Table: see text]
Randomized phase II trial of two dosing schedules of BI 2536, a novel Plk-1 inhibitor, in patients with relapsed advanced or metastatic non-small-cell lung cancer (NSCLC)
Authors: J. Von Pawel, M. Reck, W. Digel, C. Kortsik, M. Thomas, N. Frickhofen, M. Schuler, B. Gaschler-Markefski, G. Hanft, M. Sebastian
Journal: Journal of Clinical Oncology (2008)

8030 Background: BI 2536 is a novel, highly selective, potent inhibitor of Polo-like kinase 1 (Plk1), a key regulator of mitotic progression; BI 2536 has demonstrated favorable tolerability and antitumor activity in Phase I trials. We investigated the efficacy, safety and pharmacokinetics (PK) of two dosing schedules of BI 2536 in patients with relapsed advanced or metastatic NSCLC. Methods: Patients with NSCLC Stage IIIB/IV and ECOG performance status ≤2 who had relapsed after 1st- or 2nd-line therapy were randomized to receive BI 2536 on Day 1 (200 mg) or Days 1–3 (3×50 mg/3×60 mg) of 21-day treatment courses. Primary endpoint was objective response according to RECIST. Secondary endpoints were progression-free and overall survival (PFS and OS). Adverse events (AEs) were evaluated using common terminology criteria for AEs. Doses were escalated every other treatment course if well tolerated. Plasma was collected for population PK analysis. Results: Of 95 patients, four had partial responses (three in the Day-1 and one in the Day 1–3 schedule). PFS and OS were 58 days (95% CI: 48–85) and 189 days (95% CI: 176–304; 47 patients censored). Grade 4 neutropenia occurred in 36% of patients; one had febrile neutropenia. Two deaths (due to sepsis and pulmonary hemorrhage) were potentially related to BI 2536. Common, generally mild, non-hematological AEs were fatigue (30%) and nausea (26%). Preliminary model-based PK analyses indicate BI 2536 is a high-clearance compound (>1,000 mL/min) which quickly distributes in multiple compartments in a large volume of distribution (>1,000 litres). Estimated elimination half-life was >20 hours. Conclusion: Preliminary results show moderate efficacy and acceptable safety of BI 2536 monotherapy in relapsed NSCLC, thus validating Plk1 as a promising target for this novel class of antiproliferatives. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Boehringer Ingelheim, Boehringer Ingelheim Pharma GmbH & Co. KG Boehringer Ingelheim Pharma, Boehringer Ingelheim Pharma GmbH & Co. KG, Hoffman-La Roche, Lilly Oncology Bayer HealthCare, Boehringer Ingeheim Pharma, Hoffman-La Roche, Lilly Oncology
Mucinous neoplasms of the appendix: A single-center experience.
Authors: Sharon Guo, Maura Meredith Barry, Cristina Hajdu, Deirdre Jill Cohen
Journal: Journal of Clinical Oncology (2013)

368 Background: Appendiceal neoplasms are poorly understood and represent less than 0.5% of all gastrointestinal cancers. We describe the presentation, pathologic characteristics, and treatment interventions that may have affected patient (pt) outcome. Methods: This is a retrospective review of pts with appendiceal neoplasms treated at NYU Medical Center and/or NYU Cancer Center between 2002-2011. Pt demographics and medical history were collected, including pathology reports, operative findings, imaging studies, treatment and outcomes. Results: 41 consecutive pts with varying stages of appendiceal cancer were identified (70.7% female, median age 57). Most common presentations included: 15 (36.6%) gynecologic complaints, 12 (29.2%) acute appendicitis, and 11 (26.8%) abdominal symptoms. Histologic subtypes were 27 (65.9%) mucinous cystadenomas and 14 (34.1%) adenocarcinomas of which 12 (29.3%) were mucinous adenocarcinoma and 2 (4.9%) were signet cell mucinous adenocarcinoma. Distribution of stages was: 27 (65.9%) stage 0, 2 (4.9%) stage I, 2 (4.9%) stage IIA/B, 6 (14.6%) stage IVA, and 4 (9.8%) stage IVB. All pts underwent one or more of the following procedures: appendectomy (n=39), colectomy (n=9), bilateral salpingo-oophorectomy (n=4), other (n=1). 9 of 10 stage IV pts underwent debulking, of those 2 had suboptimal debulking. 1 stage II pt and 4 stage IV pts (all mucinous adenocarcinoma subtype) received hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin-C (all female, median age 39). In contrast, 6 stage IV pts (2 signet cell adenocarcinoma, 4 mucinous adenocarcinoma subtypes) did not receive HIPEC (67% female, median age 80). 1 pt received systemic 5FU based chemotherapy in addition to HIPEC (female, age 39). Median overall survival (mOS) for all pts ≥ stage II is 32 months. mOS in pts ≥ stage II who did not receive HIPEC is 8 mo whereas mOS in pts ≥ stage II who received HIPEC has not been reached. Conclusions: Appendiceal cancer is frequently detected as an incidental finding for gynecologic and abdominal complaints or presents as acute appendicitis. Surgery is the mainstay of treatment for this disease. Additional therapy including HIPEC may be of benefit in select advanced stage patients.
The effect of single weekly paclitaxel in heavily pretreated ovarian cancer patients and its antiangiogenic effects
Authors: K. Kudoh, Y. Kikuchi, T. Kita, M. Takano, K. Saito, K. Fujii, N. Sasaki
Journal: Journal of Clinical Oncology (2005)

5115 Background: We have reported that single weekly paclitaxel has moderate activity in heavily pretreated ovarian cancer patients and is associated with a favorable toxicity profile. The purpose of this study was to confirm not only antitumor but also antiangiogenic effects of weekly paclitaxel. Methods: Although 39 patients were enrolled, 37 patients with recurrent or persistent ovarian cancer previously treated with between one and three chemotherapeutic regimens containing platinum were eligible. Patients had measurable or assessable disease defined by clinical exam, radiographic studies, or serum CA 125. One cycle of treatment consisted of paclitaxel 80 mg/m2/week in 1-h infusion, 3 weeks on, 1 week off, and repeated at least twice. Two patients were withdrawn because of refusal of further treatment for neuropathy after the first cycle. Clinical responses were defined by established criteria. VEGF and IL-8 levels in serum before and 3 weeks after chemotherapy were measured, using ELISA assay. Results: Thirty-seven patients were included in this intent-to-study. The overall clinical response rate was 45.9% (5 complete responses, 12 partial responses). The clinical response rate in patients with measurable tumor was 25.0% (2 complete responses, 1 partial response), while that in patients without measurable tumor and with assessable CA 125 levels was 56.0% (3 complete responses, 11 partial responses). Clinical response rate in patients with chemotherapy-free interval more than 6 months had about twice higher than that in patients with chemotherapy-free interval less than 6 months. The clinical response rate by number of prior regimens revealed that as number of prior regimens increases, the response rate decreases. Although serum VEGF and IL-8 levels in patients with progressive disease remained high, those in patients with not only response but also stable disease to weekly paclitaxel decreased within normal range. Conclusions: It is noteworthy that weekly paclitaxel has not only significant antitumor activity but also antiangiogenic activity in heavily pretreated ovarian cancer patients. No significant financial relationships to disclose.
Staging of gastric cancer: Comparison of post-operative pathologic staging to pre-operative CT and endoscopic ultrasonographic staging.
Authors: Sung Min Jung, Dae Young Cheung, Jin Il Kim, Jae J. Kim, Sang Woo Lee, Hyun Chae Jung
Journal: Journal of Clinical Oncology (2016)

11 Background: Stomach CT and endoscopic ultrasonography are used for evaluating pre-operative staging of gastric cancer. The aim of this study was to compare the pre-operative CT and endoscopic ultrasonographic staging to post-operative pathologic staging. Methods: We reviewed medical records of 567 patients with gastric cancer from 2012 to 2015, and compared their pre-operative CT staging to post-operative pathologic staging. Among the 567 patients, 149 patients underwent pre-operative endoscopic ultrasonographic staging, so we compared their pre-operative endoscopic ultrasonographic staging to post-operative pathologic staging. We also investigated lymph node metastasis in 146 patients with gastric cancer invading submucosa, planning to undergo endoscopic submucosal dissection. Results: The numbers of patients diagnosed as T1, T2, T3, T41, and T4b by pre-operative CT staging were 327, 97, 93, 46, and 4, respectively. However, the numbers of patients diagnosed as T1, T2, T3, T41, and T4b by post-operative pathologic staging were 208, 153, 53, 83, 62, and 8, resulting the pre-operative CT staging to be under-estimated. Similarly, pre-operative endoscopic ultrasonographic staging was also under-estimated, as although 48, 67, 32, and 2 patients were diagnosed as T1a, T1b, T2, and T3, respectively, by the pre-operative endoscopic ultrasonographic staging, post-operative pathologic staging revealed 72, 55, 13, 7, and 2 patients. In patients with gastric cancer invading submucosa (sm), there were 56 patients with sm1 invasion, 32 patients with sm2 invasion, and 91 patients with sm3 invasion. Lymph node metastasis was observed in 7 patients with sm1 invasion, 3 patients with sm2 invasion, and 22 patients with sm3 invasion. Poorly cohesive gastric cancer was the most common pathologic diagnosis in patients with metastatic lymph node. Conclusions: Physicians should keep in mind that pre-operative stomach CT and endoscopic ultrasonographic staging can be under-estimated compared to post-operative pathologic staging. Also, patients with poorly cohesive adenocarcinoma had more lymph node metastasis than patients with differentiated adenocarcinoma.
A phase II and pharmacodynamic trial of RO4929097 for patients with recurrent/progressive glioblastoma.
Authors: D. M. Peereboom, J. N. Rich, J. G. Supko, K. Lamborn, X. Ye, A. E. Sloan, M. Prados, S. A. Grossman
Journal: Journal of Clinical Oncology (2011)

TPS135 Background: Patients with recurrent glioblastoma (rGBM) have a 6-month progression-free survival (PFS6) of only 10-15%. Cancer stem-like cells (CSCs) are a subset of cells that are capable of self renewal and differentiation within a tumor. These properties are felt to be a major cause of resistance to chemotherapy and radiotherapy. Furthermore, CSCs promote tumor angiogenesis. Therefore, CSCs are an attractive target for therapy of GBM. Proliferation of CSCs occurs via several pathways. One of the major signaling pathways is Notch. Elevation of Notch signaling imparts a tumor growth advantage by keeping tumor cells in a stem cell-like proliferative state. Expression of Notch is critical for survival and proliferation of human gliomas. Gamma secretase (GS) cleaves the Notch receptor as part of normal Notch function and is thus a critical enzyme in the Notch pathway. Therefore, disruption of the Notch pathway by inhibition of GS is a logical treatment strategy for patients with GBM. RO4929097 is an oral small molecule inhibitor of GS. This phase II and pharmacodynamic study will assess the efficacy of RO4929097 against rGBM and will include biomarker assays on freshly resected GBM samples from patients receiving this agent. Methods: Two groups of adults with contrast-enhancing rGBMs and no prior GS inhibitor treatment will be eligible: Group A - 40 non-surgical patients who will receive RO4929097, 20 mg 3 days on/4 days off with a primary endpoint of PFS6 on a standard phase II design; and Group B- 20 patients who will receive drug before and after resection of rGBM. Group B patients must have tumor > 2.5 cm in diameter. These patients will receive drug pre-op: 10 mg/d x 6 days; and post-op: 20 mg 3 days on/4 days off until progression. Fresh tumor from Group B patients will be assayed for neurosphere generation, expression levels of Notch pathway components and downstream targets and survival of mice bearing fresh tumor tissue. The goal is to achieve a 25% reduction of neurosphere generation when compared to a contemporaneous group of rGBM patients. If successful, these studies will provide proof of principle that CSC-targeted drug therapy can cross the blood tumor barrier and can alter the molecular and functional aspects of CSCs.
Targeted agent use in patients with cancer at the end of life.
Authors: David Hui, Meghan Sri Karuturi, Kimberson Cochien Tanco, Jung Hye Kwon, Sun Hyun Kim, Tao Zhang, Jung Hun Kang, Gary B. Chisholm, Eduardo Bruera
Journal: Journal of Clinical Oncology (2012)

215 Background: Chemotherapy use at the end of life is considered an indicator of poor quality of care. The use of targeted agent has not been well characterized. In this study, we determined the frequency and predictors of targeted therapy use in the last 30 days of life. Methods: All adult patients residing in the Houston area who died of advanced cancer between September 1, 2009 and February 28, 2010 and had contact with our institution within the last three months of life were included. We collected baseline demographics and data on chemotherapy and targeted agents. Results: 816 patients were included: average age 62 (range 21 to 97), female 48% and White 61%. The median interval between the last treatment and death was 47 (interquartile range 21 to 97) days for targeted agents and 57 (26 to 118) days for chemotherapeutic agents. 116 (14%) patients received targeted agents and 147 (18%) received chemotherapy within the last 30 days of life. 43 (5%) patients received targeted agents had concurrent chemotherapy. The most common targeted agents in the last 30 days of life were erlotinib (n=25), bevacizumab (n=20) and rituximab (n=11). In multivariate analysis, younger age, hematologic, and lung malignancies were associated with increased targeted agent use in the last 30 days of life (Table). Conclusions: Targeted agents were used as often as chemotherapy at the end of life, particularly among younger patients and those with hematologic malignancies. Guidelines on targeted therapy use at the end of life are needed. [Table: see text]
Oncology Medical Home to address challenges in breast cancer care delivery.
Authors: J. R. Trosman, C. B. Weldon, A. B. Benson, W. J. Gradishar, J. C. Schink
Journal: Journal of Clinical Oncology (2011)

e16641 Background: Care fragmentation and poor coordination in oncology negatively impact patient outcomes (IOM 2001, 2005). The Patient Centered Medical Home (PCMH) promises improved coordination of primary and chronic care (IOM, 2008). We previously identified unique challenges in breast cancer care coordination (Schink JC, ARM-1162-2010). Here we explored the distinct characteristics of Oncology Medical Home (OMH) which may address these challenges. Methods: 59 semi-structured interviews with: breast cancer care providers (n=26), patients (n=9), executives (n=24) from 5 major payers. Three multi-disciplinary focus groups included a subset of interviewed individuals (n=17, n=25, n=15). Interviews and focus groups were recorded, transcribed and analyzed according to the framework approach. Results: Theme analysis identified 4 unique characteristics of OMH: 1. OMH should have a lead physician—oncologist or breast surgeon (early stage patients)—for the entire episode of cancer care, then transfer survivors to PCMH. 2. Lead physician facilitates the cross-domain care team from diagnosis through survivorship, including surgery medical oncology, radiology, supportive and primary care. 2. Care and team should be managed as a project, with key events sequenced and timed in a plan, by a care project manager (e.g. APN). 4. OMH requires a unique reimbursement model to incentivize team participation and coordination. Patients strongly encouraged the lead physician feature. Providers suggested all OMH features. Half the payers were not certain of specific OMH features, but most recognized the need for a new reimbursement model. Conclusions: Oncology has unique care coordination and reimbursement challenges. An Oncology Medical Home may address these challenges, but should incorporate features distinct to cancer care and be facilitated by redesigned provider reimbursement. Implementation of OMH may be challenging, but could revolutionize care for cancer patients. OMH pilots will inform implementation and dissemination. OMH characteristics Providers Payers Patients Oncologist or surgeon lead physician 73% 46% 89% Cross-domain care team 81% 63% 78% Care project plan 73% 38% 67% Unique reimbursement model 85% 88% 33%
Histologic and genotypic re-evaluation of non-small cell lung cancer (NSCLC): A monocentric study.
Authors: Tiziana Vavalá, Marco Busso, Luisella Righi, Simona Vatrano, Susanna Cappia, Diego Sardo, Simonetta Grazia Rapetti, Andrea Veltri, Mauro Papotti, Giorgio Vittorio Scagliotti, Silvia Novello
Journal: Journal of Clinical Oncology (2014)

e19083 Background: Mechanisms of resistance are responsible for the progression of the disease both in patients (pts) with lung cancer treated with cytotoxic drugs and in those receiving targeted therapies. Histological and genetic analyses on tissue samples performed after treatments could be relevant to define subsequent strategies. Methods: NSCLC pts with adequate archival tissue samples before and after at least one treatment have been evaluated from July 2006 to December 2013 in a single institution. All had ECOG Performance Status of 0 and IIA-IV stage at diagnosis, median age of 51 years. After histological examination, mutational analyses for EGFR, K-RAS, PIK3CA, B-RAF and HER2 genes were performed using pyrosequencing and Real time PCR was used to detect EGFR resistance mutation. ALK and MET genomic rearrangements were tested by FISH. Results: 33 cases were analysed. Diagnoses were re-confirmed in all but one case (3%) in which morphological and immunophenotypical features of small cell lung cancer were detected. At the first biopsy, EGFR activating mutations were identified in 15/33 (45%) pts and 12/15 (80%) of them maintained activating mutations at the second biopsy with 5/12 (42%) having also a pT790M mutation (4/5 (80%) de novo and 1/5 (20%) already detected at baseline). ALK rearrangement was identified in 6/33 (18%) pts and it was mutually exclusive with EGFR mutations, both at the first and the second biopsy. MET amplification was evidenced at the first biopsy in 5/33 (15%) pts (3/5(60%) of these were also EGFR mutated) and in 11/33 (33%) pts at the second one. K-RAS mutations were found in 5/33 (15%) and in 6/33 pts (4 maintained and 2 de novo) at the first and second biopsy, respectively. PIK3CA mutations were present in 2/33 (6%) pts at the first and only one was maintained at the second biopsy. BRAF mutation was detected at the second biopsy in 2/33 (6%) pts. No HER2 mutations were found. Conclusions: This study confirms a relevant percentage of molecular profile changes (up to 61%) after therapy and underlines the value of repeated evaluations for molecular diagnostic purposes, in order to design appropriate tailored therapies, even after acquisition of various resistance mechanisms.
Feasibility and potential benefit of neoadjuvant chemotherapy for colorectal liver metastasis: A single-centered retrospective study.
Authors: K. Kataoka, A. Kanazawa, A. Nakajima, A. Yamaguchi, S. Tuyuki, A. Arimoto, Y. Kohno
Journal: Journal of Clinical Oncology (2011)

465 Background: Recently, several papers have reported the advantage of neoadjuvant chemotherapy for liver limited metastatic colorectal cancer. In these papers, most study groups used criteria for non-resectability due to size and/or number of metastases. Our criteria for resectability of colorectal liver metastases (CLM) depends on the size of remnant liver volume (&gt;30%) and expected function after the removal of all metastases. Then, we assessed the feasibility and potential benefits of chemotherapy administered before surgery to patients with CLM retrospectively. Methods: From January 2007 to April 2010, 67 chemotherapy-naive patients were diagnosed as CLM without extra-hepatic metastases. After chemotherapy, we assessed the resectability with radiological examination.Then, each case was divided in two groups, resected group and unresected group. Overall survival, median disease-free survival and postoperative complications were analyzed. Results: 63 patients received oxaliplatin-based combination regimen and 4 patients other regimen. 30 patients (resected group) received R0 resection and 37 patients (unresected group) were considered as unresectable. No serious postoperative complications were observed. Overall survival was significantly higher in resected group than in unresected group (42.3 month and 29.1 month; P&lt;0.001). Median disease-free survival was 18.8 months in resected group (95% CI:3.02 to 31.33). According to our retrospective review, resectable cases increased from 28 of 67 patients at baseline to 33 after chemotherapy (including 3 cases considered as CR after chemotherapy only). Conclusions: Intensive treatment with neoadjuvant chemotherapy for CLM is well tolerated. Curative surgery improved significantly overall survival in patients with CLM. Neoadjuvant chemotherapy such as mFOLFOX6 may lead to increased resectability but do not increase postoperative complications. For most patients with resectable CLM, neoadjuvant chemotherapy should be considered the standard treatment. No significant financial relationships to disclose.