tbuckley/cabot-search huggingface dataset:
Multicenter phase II study evaluating docetaxel (D) and cisplatin (C) as an induction regimen prior to surgery or radiochemotherapy (RCT) with D, followed by adjuvant D in chemonaive patients with NSCLC: TAX-AT1–203
Authors: R. Greil, W. Pfeifer, N. Vetter, J. Eckmayr, O. Burghuber, W. Hilbe, T. Schmid, G. Gastl, A. Mohn-Stauder
Journal: Journal of Clinical Oncology (2007)

7702 Background: This phase II study evaluated operable and unresectable patients (pts) treated with induction chemotherapy with DC to assess the response rate and conversion to resectability. Furthermore, the feasibility and efficacy of radiosensitizing with D was tested in unresectable pts undergoing RCT. The feasibility of adjuvant D was investigated in all patients. Study Design: Pts with stages II, IIIA and IIIB NSCLC were treated with 3 cycles of 3-wkly neoadjuvant D (75 mg/m 2 d 1) and C (40 mg/m 2 d1, 2). Within 4 wk after induction, pts were either resected or treated with RCT (2 Gy × 5d for 6 wk) and D 20 mg/m 2 wkly × 6 cycles. Within 4–8 wk after definitive RCT or surgery, 3 cycles of adjuvant D 75 mg/m 2 q3wk were initiated. Adjuvant RT was allowed in non-R0 resected cases. The primary endpoint was response rate to induction; secondary endpoints included resectability after induction, progression-free survival, overall survival, and safety. Results: 77 pts were included: age 60 yr [46–76 yr], males 78%, stages (II/IIIA/IIIB: 8%/39%/52%), primary resectability n=22 (29%), primary unresectability n=55 (71%). 59 patients were evaluable after induction chemotherapy, of whom 66% achieved a PR, 23% had stable disease, and 10% progressed. The PR rate was 73% in initially resectable and 63% in initially unresectable pts. 67 pts were evaluable for resectability. 28/39 (72%) of PR patients were resectable. As a result of induction therapy, 19 pts (25%) became resectable, 18 (24%) remained resectable, 27 (35%) remained unresectable, and 3 (4%) became unresectable. Treatment had to be stopped in 11 pts during induction. Three pts, primarily unresectable (4%) died of toxicity. 53% of patients had a grade 3 or 4 toxicity. In evaluable pts, the median PFS was 350 [80–1495] days vs 192 [21–989] days for resectable and unresectable pts after induction, respectively, and overall survival was 491 vs 303 days. Conclusions: DC induction chemotherapy resulted in a promising PR rate and rate of secondary resectability. The toxicity is substantial. Results of efficacy and toxicity of radiosensitizing and adjuvant D are pending. No significant financial relationships to disclose.
Real-Time Quantitative Polymerase Chain Reaction (RQ-PCR) Monitoring of Minimal Residual Disease (MRD) in Core Binding Factor Acute Myeloid Leukaemia (CBF AML).
Authors: Steven W. Lane, Russell Saal, Peter Mollee, Andrew Grigg, Kerry Taylor, John Francis Seymour, Glen Kennedy, Bronwyn Williams, Mark Jones, Karen Grimmett, Vanessa Griffiths, Devinder Gill, Matthew Hourigan, Paula Marlton
Journal: Blood (2006)
Relapsed Childhood High Hyperdiploid Acute Lymphoblastic Leukemia: Genome-Wide Screening Reveals the Presence of Preleukemic Ancestral Clones and the Secondary Nature of Microdeletions and RTK-RAS Mutations.
Authors: Josef Davidsson, Kajsa Paulsson, David Lindgren, Henrik Lilljebjörn, Tracy Chaplin, Erik Forestier, Mette K Andersen, Ann Nordgren, Richard Rosenquist, Thoas Fioretos, Bryan D Young, Bertil Johansson
Journal: Blood (2009)
PML-RARα isoform at diagnosis is associated with disease-free survival (DFS) in patients enrolled in the intergroup trial (C-9710) for treatment of acute promyelocytic leukemia (APL)
Authors: W. Stock, B. Moser, D. A. Sher, E. Schachter-Tokarz, M. Myers, B. L. Powell, C. D. Bloomfield, D. Bucci, M. S. Tallman, R. A. Larson, R. E. Gallagher
Journal: Journal of Clinical Oncology (2006)

6504 Background: Refinement of prognostic groups using molecular genetic features of the disease may facilitate the design of future risk-adapted trials for APL. Previous analyses of the prognostic value of PML-RARα transcript levels and isoform type have generated conflicting results. We sought to determine the clinical significance of measuring PML-RARα transcript level at the time of diagnosis using real-time quantitative RT-PCR (RQ-PCR) of the long (L) and short (S) isoforms of the fusion gene. Methods: PML-RARα transcript levels were measured in pretreatment bone marrow (BM) and/or paired blood (B) samples of 139 patients (pts) with newly diagnosed APL registered to C-9710, the intergroup phase III randomized study of concurrent tretinoin and chemotherapy with or without arsenic trioxide as initial consolidation therapy. Transcript levels were expressed as the normalized quotient (NQ) of PML-RARα/ABL or PML-RARα/GAPDH. Correlations between pre-treatment NQ values and other pre-treatment characteristics including age, presenting WBC and platelet count, and L or S isoform were explored. Results: Pre-treatment NQ values using ABL vs. GAPDH showed significant correlation (p &lt; 0.0001). Pre-treatment transcript levels in B and BM for 57 pts with S-form were significantly higher than 82 L-form patients (p = 0.02) when NQ was determined using GAPDH as the control gene (but not with ABL). With a median follow-up of 24.3 months for all patients, there have been 19 events. Median DFS for either isoform has not been reached, however, DFS was significantly shorter for patients with S-isoform compared to those with L-isoform (p = 0.017) with an estimated hazard ratio of 3.28. Using a multivariate proportional hazard model, no other significant relationships were found between DFS and NQ level at diagnosis, age, presenting WBC or platelet count. Conclusions: The S-isoform of the PML-RARa fusion gene was associated with shorter DFS in a subset of patients entered onto C-9710. If confirmed in a larger cohort of C-9710 pts, presence of the S-isoform should be considered as a high-risk feature in the design of future risk-adapted treatment strategies for APL. No significant financial relationships to disclose.
A phase II trial of SNS-595 in women with platinum resistant epithelial ovarian cancer
Authors: W. P. McGuire, H. W. Hirte, U. A. Matulonis, R. T. Penson, A. Husain, P. J. Hoskins, J. Michels, G. Michelson, A. Chiang, C. A. Aghajanian
Journal: Journal of Clinical Oncology (2008)

5582 Background: SNS-595 is under clinical investigation in acute leukemia and ovarian cancer. Clinical responses have been observed in these indications, and in non-small cell and small cell lung cancers. SNS-595 is a replication-dependent DNA damaging agent that causes irreversible G2 arrest and apoptosis via DNA intercalation and topoisomerase II inhibition. A phase 2 study of single agent SNS-595 in ovarian cancer was initiated based on phase 1 clinical activity in patients (pts) with ovarian cancer, including one partial response (PR). Methods: Pts had advanced platinum resistant (progressed during or relapsed within 6 months of platinum based therapy) epithelial ovarian cancer who had progressive disease after 1 or 2 prior platinum containing regimens; pts could have received an additional biologic or non-platinum therapy after becoming platinum-resistant. A GOG PS of 0–1 and adequate hematologic, hepatic and renal status were required. Pts received 48 mg/m2 SNS-595 by 10 minute IV infusion on Day 1 of a 21-day cycle. Results: Enrollment is completed at 48 mg/m2 with 55 women treated of 57 enrolled; 35 have sufficient follow-up to yield relevant safety results. Median age was 60.5 y (range 33–82 y) with majority Caucasian (n=30); African American (n=2); Asian family origin (n=4). Median number of prior therapies was 2 (range 1–4); 17 pts previously failed pegylated liposomal doxorubicin (PLD) therapy and 18 pts were PLD- naïve. SNS-595 infusions were well tolerated. Dose reductions/delays were primarily due to neutropenia; incidence of febrile neutropenia was <20%. The most common adverse events were nausea and fatigue, but these were generally mild-moderate. Best response data in the database are available for 22 pts: two confirmed PR, 1 unconfirmed PR, 16 SD, 3 PD were observed (Overall response rate 14%). All 3 pts with PRs failed 2 prior platinum-containing regimens and 2 of the 3 also failed PLD within 6 months. Conclusions: SNS-595 demonstrated objective responses in platinum and PLD resistant ovarian cancer and was generally well tolerated. Enrollment at 48 mg/m2 is completed and follow-up is ongoing. The low incidence of febrile neutropenia and objective responses at 48 mg/m2 supports ongoing evaluation of SNS-595 at an increased dose Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Sunesis Sunesis
Result of HER2 status in Japanese metastatic gastric cancer: Prospective cohort study (JFMC44-1101).
Authors: Kazuhiro Nishikawa, Keisho Chin, Atsushi Nashimoto, Akira Miki, Hiroto Miwa, Akira Tsuburaya, Tamon Miyanaga, Takuo Hara, Ryoji Fukushima, Makio Gamoh, Norimasa Fukushima, Takeshi Sano, Yasuhiro Kodera, Yoshihiro Kakeji, Satoshi Morita, Junichi Sakamoto, Shigetoyo Saji, Kazuhiro Yoshida
Journal: Journal of Clinical Oncology (2013)

10 Background: Randomized phase III (ToGA trial) has demonstrated that the addition of trastuzumab to standard chemotherapy improved overall survival in patients (pts) with HER2-positive metastatic gastric cancer (mGC). In screening of the ToGA trial, HER2 positivity rate was 22.1 % in total, but the rates varies between countries. Therefore, to determine the HER2 incidence rate in Japanese mGC, we planned prospective cohort study JFMC44-1101. Methods: JFMC44-1101 is a multicenter epidemiological trial assessing HER2 status in Japan. Patients with histologically confirmed gastric adenocarcinoma, not suitable for curative resection were eligible. HER2 status was centrally assessed both immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) using formalin fixed paraffin embedded (FFPE) tissues from tumor. HER2 positive is defined as either IHC3+ or FISH+ in accordance with ToGA trial. Overall and subgroup estimates calculated with 95%CI. Results: Between September 2011 to June 2012, 1466 pts were registered from 157 sites. Patients characteristics were; gender (M/F):1044/422, median age (min-max): 68 (25-99), advance / recurrence: 1068 / 398. Samples are 768 from biopsy and 698 from excision. In August 2012, 1427/1466 pts were assessed. Overall, HER2 positivity was 20.5% (293 pts). Each IHC status (0/1+/2+/3+) with FISH+ was 3.0% / 11.3% / 46.9% / 97.2%, respectively. The frequency of IHC 0/1+ with FISH+ was almost as high as IHC 2+ with FISH+ (5.6%/4.2%). HER2 positivity rate of background factors were; male/female:23.6%/14.3%, biopsy/ excision: 22.7%/19.0%, advance / recurrence: 21.6%/17.6%. Conclusions: JFMC44-1101 confirmed the incidence of HER2 positivity in Japanese mGC. HER2-positivity rate and HER2 status were similar to the ToGA screening population. Clinical trial information: UMIN000006190.
The coverage of cancer in the Israeli press
Authors: A. Kuten, N. Haim, E. Lev, G. Weimann
Journal: Journal of Clinical Oncology (2004)

6095 Background: Cancer, being a terminal and often incurable disease, is a source of fear and concern for people. One of the most important sources for medical information in general, and cancer specifically, is the mass media. The media can shape beliefs regarding health and influence people's decision making. The main hypothesis guiding this study, based on the theoretical framework of cultivation research, is that there will be considerable differences between media coverage and medical data regarding cancer in the Israeli population in terms of the types of cancer reported, and the emphasis on death in the context of the disease. Methods: A systematic content analysis was applied to test these hypotheses, examining all the press reports published in Israel's most popular daily newspapers during the year 2000. Data from the Israeli Ministry of Health was used for comparison with media reports. Results: The findings of the study are in accordance with the main hypothesis and show that media portrayals of cancer are not always reflecting the medical reality. Several explanations are offered to explain these findings, focusing mainly on the nature of news making and media selection as well on the impact of various interest groups such as pharmaceutical companies, hospitals, laboratories, oncology departments, and various organizations trying to promote awareness and raise funds for research. Conclusions: The findings of this study join a wide range of studies in different areas of human knowledge and judgments that have documented processes of constructing “mass-mediated realities” but in the case of a fatal disease the findings may have acute implications. No significant financial relationships to disclose.
Total chemotherapy cost in NSCLC across Europe: Distribution of cost factors observed in three randomised clinical trials
Authors: A. Kielhorn, S. Bhalla, G. Stynes, D. Tilden
Journal: Journal of Clinical Oncology (2004)

7225 Background: Economic analysis of randomized trials and meta-analyses have demonstrated that platinum-based therapy increases survival in NSCLC and is cost effective. However, limited healthcare budgets in most EU healthcare systems are leading to measures to contain or control expenditure on a national or hospital level. The discussion of treatment cost is dominated by data on the cost of the cytotoxic agent, not the total treatment cost. However, for centres where the chemotherapy is administered and the adverse events are treated, total treatment cost per patient should be considered. The present study aimed to determine the percentage of chemotherapy agent to total average treatment cost per patients across the UK, Germany, France, Italy and Spain. Methods: A retrospective analysis based on three comparative randomised clinical trials with platinum doublets (Schiller et al., 2002, Comella et al., 2000, Scagliotti et al., 2002) was performed from the viewpoint of the respective healthcare systems (third-party payer). Only direct costs were included. Costs included chemotherapy, namely the cost of the novel agent, the platinum agent, administration, concomitant medications and all other cost items. The analysis excluded the costs for medical professionals and laboratory testing. The prices were from 2003. Results: Overall the cost of the chemotherapy agent as part of the total treatment cost was 60% and ranged from 47% (Italy) to 70% (Spain). The cost of administration varies considerably from 13% (Germany) to 35% (France). This difference may be based on the challenge to capture and quantify the cost items related to administration in a systematic way across different healthcare systems. Conclusion: The cost of chemotherapy agents represent on average 60% of the total cost of chemotherapy treatment in advanced NSCLC in 5 EU healthcare systems. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Eli Lilly
Abstract 19664: Molecular Mechanisms of Gα12 Regulated E-cadherin Shedding in Epithelial Cells
Authors: Jen Xu, Yong Wu, Suyang Li, Kenneth Lim, Tianqing Kong, Tzongshi Lu
Journal: Circulation (2014)

Introduction and hypothesis: E-cadherin plays an important role in maintaining the integrity of cell polarity and cell junctions. It is one of the major proteins that forms part of the polycystin-1 (PC1) complex in renal epithelial cells. We previously showed that deletion of the PC1-regulated protein, Gα12, protected kidneys from development of kidney cysts induced by Pkd1 inactivation and activation of Gα12 increased the shedding of E-cadherin in autosomal dominant polycystic kidney disease (ADPKD). The objective of this study was to determine the molecular mechanisms by which Gα12 regulates E-cadherin shedding. Methods: We analyzed polycystic kidneys from human and from Pkd1 knock-out mice. Using Madin-Darby canine kidney (MDCK) cells, we developed a Pkd1 deletion in vitro model using Pkd1 siRNA. Results: Our data shows that Pkd1 deletion caused accumulation of cleaved E-cadherin fragment in renal cystic fluid in both human polycystic kidneys and in our mice model. In addition, we found that activation of Gα12 increased the active form of ADAM10, the cleavage protein for E-cadherin in both human and mice polycystic kidneys, in vivo. In our MDCK cellular three-dimensional culture system, Gα12 activation promoted cyst formation and this phenomenon was inhibited by ADAM10 knockdown. Furthermore, knockdown of ADAM10 abolished the shedding of E-cadherin caused by Gα12 activation. These data indicate that ADAM10 is the major sheddase for cleavage of E-cadherin caused by Gα12 activation. Conclusion: Our results demonstrate that Gα12 activation increases ADAM10 activity and promotes the ectodomain shedding of E-cadherin, which is an important mechanism in the development of kidney cysts induced by Pkd1 deletion in ADPKD.
Carcinoembryonic Antigen in Normal Human Saliva2
Authors: F. Martin, J. Devant
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Carcinoembryonic Antigen in Normal Human Saliva Get access F. Martin, F. Martin Laboratoire de Médecine Experimentale, Faculte de Médecine, Boulevard Jeanne d'Arc, 27 033 Dijon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar J. Devant J. Devant Laboratoire de Médecine Experimentale, Faculte de Médecine, Boulevard Jeanne d'Arc, 27 033 Dijon, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 5, May 1973, Pages 1375–1379, https://doi.org/10.1093/jnci/50.5.1375 Published: 01 May 1973 Article history Received: 14 December 1972 Accepted: 12 January 1973 Published: 01 May 1973
Correlation between quantitative HER2 protein level and the risk of brain metastasis (BM) in patients (pts) with metastatic breast cancer (MBC) treated with trastuzumab-containing therapy.
Authors: R. Duchnowska, B. Szostakiewicz, T. Jankowski, B. Arlukowicz-Czartoryska, P. J. Wysocki, W. Huang, M. P. Bates, J. Weidler, M. Haddad, J. Jassem
Journal: Journal of Clinical Oncology (2010)

1030 Background: Breast cancer is estimated to be the second most frequent cause of BM; however biological basis of this phenomenon is not well established. Pts with HER2-overexpressing breast cancer are at greater risk for BM. This study sought to investigate the correlation between quantitative HER2 expression in primary breast cancers using a novel HER2 quantitative assay (the HERmark assay; Joensuu H. et al, 2008 SABCS, abstract 2071) and the risk of BM in a consecutive series of pts with MBC treated with trastuzumab-containing therapy. Methods: HER2/neu gene was quantified as HER2/CEP17 ratio by central lab fluorescence in situ hybridization (FISH) and HER2 protein was quantified as total HER2 expression (H2T) by the HERmark assay in 126 formalin-fixed, paraffin-embedded (FFPE) tumor samples. HER2 results were correlated with tumor histologic grade and BM. Mann-Whitney and Kruskal-Wallis tests were performed to compare HER2 results (as continuous variables) with tumor grade and BM. Results: HER mark showed 93% concordance with central FISH for categorical positive and negative assay values, excluding the equivocal cases. Higher H2T levels were associated with higher tumor grade and occurrence of BM (p=0.04 and 0.03, respectively), whereas HER2/CEP17 ratios were not (p=0.09 and 0.24, respectively). H2T levels were not significantly different between cases with soft tissue, bone, or viscera as the dominant site of metastasis. There was no significant correlation between HER2/CEP17 FISH ratio or total HER2 copy number and tumor grade or BM. Polysomy 17 (by FISH) in the absence of HER2 gene amplification did not result in higher HER2 expression as evaluated by the HERmark assay. Conclusions: These data suggest a relationship between quantitative HER2 expression levels and the risk of BM in patients with MBC. Since small molecule inhibitors of HER2 cross the blood-brain barrier as opposed to monoclonal antibodies, quantitative assessments of HER2 protein expression may facilitate the refinement of therapeutic treatment strategies for selected subpopulations of pts with HER2-positive MBC. These data require confirmation in further studies. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Monogram Biosciences
Impact of prior thalidomide (T) therapy on the efficacy of pegylated liposomal doxorubicin (PLD) and bortezomib (B) in relapsed/refractory multiple myeloma (RRMM)
Authors: P. Sonneveld, R. Hajek, A. Nagler, A. Spencer, J. Bladé, T. Robak, S. H. Zhuang, J. L. Harousseau, S. Fruchtman, R. Z. Orlowski
Journal: Journal of Clinical Oncology (2007)

8023 Background: IMIDs and proteasome inhibitors offer novel therapeutic options for patients with RRMM. T+Dex is approved for the treatment of newly diagnosed MM (Rajkumar JCO 2006). Wang et al (ASCO 2006, ASH 2006) suggested prior T exposure resulted in partial cross resistance to subsequent treatment with lenalidomide (L). Our objectives were to determine 1) whether resistance also existed to PLD+B in patients receiving prior T vs no prior T and 2) if the efficacy and safety profile of PLD+B was comparable to that previously reported with L+Dex in T failures. Methods: We performed a post hoc analysis of a previously reported phase III trial comparing PLD+B vs B alone (Orlowski ASH 2006). RRMM patients receiving ≥1 prior therapy and randomized to receive PLD at 30 mg/m 2 given on D4 of each cycle along with B at 1.3 mg/m 2 on D1, 4, 8, and 11 of every 21-day cycle were analyzed based on prior T exposure or no prior T. Treatment was continued for up to 8 cycles or for at least 2 cycles beyond a CR unless disease progression was observed or unacceptable toxicity occurred. Results: 324 patients were randomized to PLD+B (n=194 [T naïve], n=130 [T exposed]) and included in this analysis. Baseline albumin was 3.8 g/dL, 3.8 g/dL and 4.8 g/dL for the PLD+B (T naïve), PLD+B (T exposed) and L+Dex (T exposed), respectively. Baseline β 2 microglobulin was 5.2 g/dL, 5.4 g/dL and 3.7 g/dL for these groups, respectively. Conclusions: These results demonstrate that PLD+B provide a consistent efficacy benefit in both T exposed and T naïve patients with no evidence of cross resistance to prior T. Compared to L+Dex in a similar patient population with prior T exposure, PLD+B has comparable response rates and time to progression, but the risk of TVE is substantially reduced. These results should be considered when choosing treatment options for RRMM who have failed prior T treatment and confirmed in a prospective randomized study. [Table: see text] [Table: see text]