tbuckley/cabot-search huggingface dataset:
Effect on low HER2 (1+) expressing tumor cells of the trifunctional antibody ertumaxomab
Authors: M. Jäger, P. Ruf, A. Schoberth, J. Hess, H. Lindhofer
Journal: Journal of Clinical Oncology (2008)

3071 Background: Her2/neu has become an important therapeutic target for treatment of breast cancer with overexpressed Her2/neu. Currently, no approved antibody-based therapy is available for breast cancer patients with low Her2 expression (1+ or 2+/FISH neg.). Ertumaxomab is a trifunctional bispecific antibody targeting Her2 and CD3 with selective binding to activating Fcγ type I/III-receptors, resulting in the formation of a tri-cell-complex between tumor cells, T cells and accessory cells. Ertumaxomab therapy resulted in radiographically confirmed clinical responses in a phase I trial involving metastasized breast cancer patients (Kiewe et al., CCR, 12:3085, 2006). Methods: In this study, we compared tumor cell killing potency of ertumaxomab with trastuzumab using low Her2 expressing tumor cell lines of different origins (colon, breast, lung). Unstimulated PBMCs of healthy donors and the different cell lines were incubated with the respective antibodies at varying concentrations. Immune effector cells were removed after 4 days and dose response was measured by evaluating the tumor cell killing using a cell viability assay (XTT). In addition, cytokine pattern in the supernatants were analyzed. Results: Under conditions found to be optimal for trastuzumab to kill Her2 overexpressing cells, only ertumaxomab was able to eliminate the tumor cell lines that express Her2 at low level (1+). Cytotoxicity induced by ertumaxomab was observed already at concentrations as low as 1ng/ml and controls demonstrated that tumor cell lysis was dependent on the binding to Her2. In contrast to trastuzumab, ertumaxomab activity was accompanied by a Th1 type cytokine release including IL-2, IL-6, TNF-alpha and IFN-gamma underlining the unique mode of action of trifunctional antibodies. Conclusions: In conclusion, ertumaxomab was able to induce immune effector cell stimulation and cellular cytotoxicity against various tumor cell lines including Her2 low expressing cells. Thus, ertumaxomab may provide a new antibody-based therapeutic option for breast cancer patients with low level expression of the Her2 target antigen who are not eligible for trastuzumab treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration TRION Pharma, TRION Research TRION Pharma, TRION Research
Diagnosing a miscarriage
Authors: Elizabeth Anne McCarthy, Stephen Tong
Journal: BMJ (2015)

When is it safe to make the call?

The diagnosis of a miscarriage will more than likely dash the hopes and dreams of couples anticipating the life changing possibilities of a new addition to their family—a new house, extended leave from work, relief in finally appeasing grandparents-in-waiting. It is therefore paramount that clinicians get it right. Always.

It was a touch unnerving when evidence emerged around 2011 suggesting that ultrasonography criteria advocated by official bodies may be too liberal, and that they risked some viable pregnancies being misdiagnosed as miscarriages.1 2 3 4 In response, more conservative ultrasonography criteria were published as recently as 2013.5

Given these recent shifts in criteria to define something so important, it is timely that in this issue Preisler and colleagues (doi:10.1136/bmj.h4579) present a large prospective multicentre study to inform about when it is safe to make the call that a pregnancy has failed.6

Over two and a half years the team recruited 2558 women across seven early pregnancy units in the United Kingdom.6 They included women in whom it was unclear at the first ultrasound scan …
Preliminary data of a phase I-II clinical and pharmacokinetic study of plitidepsin in children with malignant tumors. On behalf of the European ITCC (Innovative Therapies for Children with Cancer) Consortium
Authors: B. Geoerger, F. Doz, E. Estlin, P. Kearns, J. Lopez-Martin, G. Vassal, S. Bezares, M. Ruiz
Journal: Journal of Clinical Oncology (2006)

9060 Background: Plitidepsin (Aplidin) is a cyclic depsipeptide isolated from the tunicate Aplidium albicans, nowadays manufactured by synthesis. It is a rapid and potent inductor of apoptosis. Phase I trials in adults explored 5 different schedules. Muscle and liver toxicities were dose-limiting; hematological toxicity was not observed at the recommended dose (RD). Methods: This is a multicentre, open-label, non-randomized phase I-II study with a dose finding stage in children with solid tumors, and two expanded cohorts in leukemia and solid tumors at the RD. Plitidepsin was administered as a 3 h iv infusion every 2 weeks (=1 cycle). The initial dose level was 4 mg/m 2 (80% of the RD in adults), with a classical escalation to 5 and 6 mg/m 2 . Results: 16 patients have been entered to date with median age 7.5 years (range 2–17). 54 cycles in 15 patients were evaluable for toxicity. 8 patients were treated at 4 mg/m 2 , five at 5 mg/m 2 and three at 6 mg/m 2 . One patient presented dose-limiting G2 myalgia lasting more than 2 weeks at 4mg/m 2 . The Maximum Tolerated Dose (MTD) has not been reached at 6 mg/m 2 . Non-hematological toxicities included G1-G2 muscle side effects: (myalgia, CPK elevation, muscle weakness), G1–2 fatigue, G3 vomiting. One G3 hypersensitivity reaction was observed without prophylactic treatment. Pharmacokinetic data are similar to those reported in adult (extensive tissue distribution, a long half-life); if any, clearance was slightly higher and half-life shorter. Partial response was observed in a pancreatoblastoma and disease stabilization in a progressive medulloblastoma. Conclusions: Plitidepsin was well tolerated in children, with muscular side effects being the most relevant toxicity observed. The MTD for the pediatric population has not yet been achieved at a dose 1.2 fold above the RD in adults. [Table: see text]
Intraperitoneal treatment of malignant ascites due to epithelial tumors with catumaxomab: A phase II/III study
Authors: S. Parsons, P. X. Murawa, P. Koralewski, E. Kutarska, O. O. Kolesnik, M. A. Stroehlein, A. Lahr, M. Jaeger, M. M. Heiss
Journal: Journal of Clinical Oncology (2008)

3000
A novel model including CXCR4 and CDK6 as potential predictive marker for docetaxel (doc) sensitivity in gastric cancer (GC)
Authors: J. Wei, L. Xie, X. Qian, G. Chen, L. Yu, Y. Ding, B. Liu
Journal: Journal of Clinical Oncology (2009)

e15548 Background: A growing body of evidence has shed light on biomarkers for chemotherapeutic agent sensitivity in gastric cancer (GC) treatment. It has been demonstrated β-tubulin Ш (TUBB3) and microtubule associated protein tau (MAPT) might be considered as potential markers for taxanes treatment. However, an integrated predictive model for docetaxel (doc) sensitivity is still needed to customized chemotherapy in gastric cancer. Methods: Doc resistant gastric cancer cell line was established by exposure to gradually increasing doc concentration on an intermittent dosage schedule. Microarray was performed to explore different gene expression levels between parental cells and resistant cells. 11 gastrointestinal cancer cell lines were used to validate gene levels by real-time quantitative PCR as well as doc cytotoxicity. Histoculture drug response assay (HDRA) was adopted to examine doc sensitivity in 25 surgically dissected GC specimens. Discrimination analyses were used to determine which linear combinations of these genes best distinguished responder patients from nonresponder patients by adding one more genes each time. Results: After functional analysis of microarray, a panel of 11 genes were further validated, which resulting 4 genes, CXCR4 (P=0.047), CDK6 (P=0.014), USP15 (P&lt;0.001) and CDH1 (P=0.001) that correlated to the doc sensitivity. The mRNA levels of CXCR4 and CDK6 were significantly higher in resistant GC specimens (P=0.0298, 0.022 respectively). A final response index including 5 genes (CXCR4, CDK6, USP15, TUBB3 and MAPT) showed potential predictive value for doc associated chemotherapy with an accuracy of 84% (P=0.001). Conclusions: A predictive model with five genes for doc therapy was generated and showed novel predictive role in doc sensitivity in GC. No significant financial relationships to disclose.
Abstract P2-01-20: The ratio and size of positive sentinel lymph nodes predicts the involvement of non-sentinel lymph nodes following completion axillary lymph node dissection
Authors: Rajiv V Dave, Muhhamed N Chauhan, Maria Ghaus, Sana Ahmed, Shiv Shapra, Joshua Marriott, Craig Sayers, Zbigniew Kryjak, Deedar Ali
Journal: Cancer Research (2015)

Abstract Background: The role of Completion Axillary Lymph Node Dissection (CALND) following positive Sentinel Lymph Node Biopsy (SLNB) is being actively debated. The involvement of our unit in the POSNOC trial (which has a no-treatment arm), has prompted a review of our unit’s CALND results, in order to examine predictors of involvement of non-sentinel lymph nodes (n-SLN), to better inform our patients during recruitment. Methods: We retrospectively analysed our experience of SNLB between July 2008 to 2013. A total of 1152 breast cancer patients underwent SLNB based on lymphoscintigraphy, intraoperative gamma probe detection, and blue dye mapping using 99mTc-nanocolloid and Patent Blue V injected peri-areola. Results: Out of 1152 SLN biopsies performed, 224 were positive for metastatic disease. 203 patients were anaesthetically capable of progressing to CALND. On univariate analysis, involved n-SLN on CALND could not be predicted by age (&amp;lt;50 years; 16/77 vs ≥50 years; 93/125, p=0.272), size of tumour (&amp;lt;50mm; 44/193 and ≥50mm; 4/10, p=0.188), procedure (mastectomy; 24/93, WLE; 24/106, p=0.444), lymphovascular invasion (22/97 vs 26/106, p=0.812), number of positive SLN (≤2; 45/196, &amp;gt;2; 3/7, p=0.213), receptor status; ER (negative; 3/13, positive 45/187, p=0.619), PR (negative; 6/28, positive 41/169, p=0.478), Her2 (negative; 43/175, positive 5/25, p=0.414), triple negative (2/8 vs 46/192, p=0.612). There was a trend toward higher incidence of positive n-SLN with increasing grade (G0-2; 28/139 vs G3; 20/64, p=0.062) and extracapsular spread (14/41 vs 32/149, p=0.073), but these did not reach statistical significance. Positive n-SLN on CALND was however predicted by macrometastases in SLN (macrometastases; 39/141 vs micrometastases; 9/62, p=0.029) and ratio of positive nodes (&amp;lt;0.5; 18/109 vs ≥0.5; 30/94, p=0.008). There were 4/224 recurrences (3 distant metastases and 1 loco-regional), which were not predicted by any of the clinicopathological variables investigated. 3 patients who recurred only had one positive node on SLNB. Conclusion In our series of more than 200 SLNB, a ratio of &amp;gt;0.5 positive SLN yield and presence of macrometastases in positive SLN, were associated with positive n-SLN on CALND. Citation Format: Rajiv V Dave, Muhhamed N Chauhan, Maria Ghaus, Sana Ahmed, Shiv Shapra, Joshua Marriott, Craig Sayers, Zbigniew Kryjak, Deedar Ali. The ratio and size of positive sentinel lymph nodes predicts the involvement of non-sentinel lymph nodes following completion axillary lymph node dissection [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-20.
Taiwanese patients with breast cancer with brain metastasis (BM) enrolled in the Lapatinib Expanded Access Program (LEAP).
Authors: C. Huang, S. Chen, M. Liu, D. Yeh, M. Hou, T. Chang, R. K. Hsieh, T. Chao, C. J. Tai, C. Tsao
Journal: Journal of Clinical Oncology (2010)

1111 Background: LEAP is an expanded access study of lapatinib in combination with capecitabine in 42 countries. The primary objective of LEAP was to provide patients with pre-approval access to lapatinib based on positive clinical data from a pivotal phase III trial. Methods: LEAP enrolled patients with ErbB2-positive, locally advanced and metastatic breast cancer (MBC) showing progressive disease following prior therapies with anthracycline-, taxane-, and trastuzumab-containing regimens. Patients received lapatinib (1,250 mg/day) and capecitabine (2,000 mg/m2/day, days 1-14, every 21 days). In this study we analyzed Taiwanese LEAP patients with BM at baseline. Brain and systemic response were assessed using RECIST criteria. Independent radiologist assessed response of BM. Results: From March 2007 to September 2008, there were 238 patients enrolled in Taiwan. We retrospectively analyzed data from 194 patients with accessible medical charts, which included 52 patients with baseline BM. Among these 52 patients, 26 (50.0%) had baseline and follow up brain computed tomography (CT). With protocol treatment 1 (3.8%) achieved complete response of brain lesions, 8 ( 30.8%) had partial response, 10 ( 38.5%) had stable disease, and 7 ( 26.9%) had progressive disease. The overall brain response rate was numerically better than the overall systemic response rate in the whole 194 subjects (34.6% vs. 22.4%, p=0.2171). The median progression-free survival (PFS) and median time to progression (TTP) of BM are significantly longer than in 194 subjects (PFS: 8.47 mon vs. 5.23 months, p=0.0054. TTP: 9.60 months vs. 5.53 months, p=0.0376). Within these 26 subjects, the tendency of better brain response than systemic response rate (34.6% vs. 25.0%, p=0.5448), longer PFS (8.47 months vs. 4.77 months, p=0.3461) and longer TTP (9.60 months vs. 5.53 months, p=0.3103) were observed. Furthermore, only 8 subjects developed BM during LEAP treatment in total 194 subjects. Conclusions: Brain is a common metastatic site for ErbB2-positive MBC patients and usually implies poor prognosis and short survival. Based on the Taiwanese LEAP experience, lapatinib plus capecitabine treatment demonstrated a significant benefit in this group of patients. No significant financial relationships to disclose.
A quantitative analysis of association between protocol deviation and adverse event in multicenter clinical trials for cancer (JCOG0704 A)
Authors: A. Sato, K. Yoshimura, I. Saito, K. Nakamura, H. Fukuda
Journal: Journal of Clinical Oncology (2008)

6585 Background: In clinical trials, deviation from a protocol has to be monitored to provide feedbacks to investigators as a part of quality control activities. However, the excessive risk of patients induced by deviation has merely been reported. Our aim is to assess quantitatively the association between deviation related to overtreatment and toxicity in multi-center cancer clinical trials. Methods: The Japan Clinical Oncology Group (JCOG) trials which were started after 1999, phase III, only using chemotherapy, and enrolled more than 100 patients are selected. Information of deviation related to overtreatment was collected from the monitoring reports of these trials, and counted in binary data (patient with or without deviations). Severe adverse event (SAE) that include Grade 4 non-hematological toxicities, death due to any course within 30 days after protocol treatment, and treatment related death were also collected from the monitoring reports, and grade 3 non-hematological toxicities (G3) were collected from study databases, and counted in binary data (patient with or without SAE or G3). In primary analysis, association between deviation and adverse event (SAE or G3) was tested by Fisher's exact test. Logistic regression is used for adjust risk factors in sensitivity analysis. Results: According to the study selection criteria, 1,515 patients from 5 JCOG trials were selected. Deviation was identified in the 304 patients (20.1%) and SAE or G3 was observed in 492 patients (32%). In primary analysis, SAE or G3 was observed in 135 patients out of 304 patients with deviation (44.4%) and in 357 patients out of remaining 1211 patients without deviation (29.5%) (Risk ratio = 1.51, 95% CI 1.29–1.76, P<0.001). This consistent result was also observed in adjusted analysis (odds ratio of deviation was 2.31, 95% CI 1.73–3.08, P<0.001). Conclusions: This study has revealed that protocol deviation related to overtreatment was strongly associated SAE or G3 risk. Intensive monitoring of deviations may minimize excessive risk of enrolled patients. No significant financial relationships to disclose.
Type-C RNA Virus Isolated From SJL/J Mice 2
Authors: Kenneth S. S. Chang, Lloyd W. Law, Tadao Aoki
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Type-C RNA Virus Isolated From SJL/J Mice Get access Kenneth S. S. Chang, Kenneth S. S. Chang 3Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar Lloyd W. Law, Lloyd W. Law 3Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Public Health Service, U.S. Department of Health, Education, and Welfare Bethesda, Md. 20014. Search for other works by this author on: Oxford Academic PubMed Google Scholar Tadao Aoki Tadao Aoki 4Viral Leukemia and Lymphoma Branch, National Cancer Institute. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 777–784, https://doi.org/10.1093/jnci/52.3.777 Published: 01 March 1974 Article history Received: 31 July 1973 Accepted: 27 October 1973 Published: 01 March 1974
Racial/ethnic disparities in estrogen and progesterone receptor phenotype and survival outcomes.
Authors: Raji Shameem, Muhammad S Hamid, Niket Sonpal, Anita Pudusseri, Robert Graham, Kevin M. Sullivan
Journal: Journal of Clinical Oncology (2014)

54 Background: The incidence of estrogen receptor (ER) and progesterone receptor (PR) phenotypes varies among different racial/ethnic groups. However, the prognostic significance of specific ER/PR phenotypes on survival in racial/ethnic groups including Asians has not been reported. Methods: The Surveillance Epidemiology and End Results (SEER) database was used to identify invasive breast cancer cases from 1988 to 2009. Groups included were: “Non-Hispanic Whites (NHW)”, “Blacks”, “Filipinos”, “Chinese”, “Japanese”, “Koreans”, “Vietnamese”, and “Asian Indian/Pakistanis (AIP)”. Cases were grouped according to ER/PR phenotype (ER+/PR+, ER-/PR-, ER+/PR-, ER-/PR+). The Kruskall-Wallis test, and the Z test were employed to examine for differences between racial/ethnic groups. Multivariate Cox proportional analyses were used to establish the weight of the age adjusted ER/PR phenotype on the prognostic significance contributing to survival. Results: In comparison to NHW, ER+/PR+ status was associated with poor outcomes in blacks (HR: 1.814, p &lt; 0.01), however improved outcomes were seen in Chinese (HR: 0.759, p &lt;0.01), Vietnamese (HR: 0.755, p &lt; 0.01), AIP (HR: 0.751; p &lt; 0.01), Koreans (HR: 0.661, p &lt; 0.01) and Japanese (HR: 0.608, p &lt; 0.01). ER-/PR- status also was associated with decreased survival in blacks (HR: 1.391, p &lt; 0.01), but improved survival in Chinese (HR: 0.793, p &lt; 0.01), Filipinos (HR: 0.787, p &lt; 0.01), Japanese (HR: 0.757, p &lt;0.01), AIP (HR: 0.751, p &lt; 0.01), Vietnamese (HR: 0.736, p &lt; 0.01), and Koreans (HR: 0.705, p &lt; 0.01). Compared to the referent NHW, ER+/PR- status in Chinese (HR: 0.765, p &lt; 0.01), Japanese (HR: 0.794, p &lt; 0.01), Filipinos (HR: 0.711, p &lt; 0.01), and Koreans (HR: 0.662, p &lt; 0.05) there was improved survival, while blacks (HR: 1.612, p &lt; 0.01) had decreased survival. Regarding ER-/PR+ status, blacks (HR: 1.464, p &lt; 0.01) had decrease survival, while only Japanese women exhibited improved outcomes (HR: 0.586, p &lt; 0.01) compared to NHW. Conclusions: For ER/PR phenotypes including ER-/PR- tumors, Asian subgroups showed favorable survival outcomes compared to NHW, while poor outcomes were seen in blacks.
AT-18 * SURVIVAL ANALYSIS OF PATIENTS WITH A PFS EVENT WHO DID NOT RECEIVE POST-PROGRESSION THERAPY IN AVAGLIO (BEVACIZUMAB [BEV] PLUS RADIOTHERAPY [RT] AND TEMOZOLOMIDE [TMZ] FOR NEWLY DIAGNOSED GLIOBLASTOMA [GBM])
Authors: T. Cloughesy, W. Wick, W. Mason, R. Henriksson, F. Saran, R. Nishikawa, A. F. Carpentier, K. Hoang-Xuan, P. Kavan, D. Cernea, A. A. Brandes, C. Revil, L. Abrey, O. L. Chinot
Journal: Neuro-Oncology (2014)

Survival analysis of patients with a PFS event who did not receive post-progression therapy in AVAglio (bevacizumab [BEV] plus radiotherapy [RT] and temozolomide [TMZ] for newly diagnosed glioblastoma [GBM])
Impact of pathological staging on survival in patients with epithelial mesothelioma treated with extrapleural pneumonectomy
Authors: D. Sugarbaker, W. G. Richards, C. A. Alsup, M. T. Jaklitsch, J. M. Corson, J. J. Godleski, L. R. Chirieac, R. Bueno, L. Zellos
Journal: Journal of Clinical Oncology (2007)

7706 Objective: There is no universally accepted staging system in malignant pleural mesothelioma (MPM). A seventeen-year single institution experience of surgically treating a large epithelial MPM cohort with extrapleural pneumonectomy (EPP) gives insight to the applications and limitations of BWH/ DFCI and AJCC staging systems. Methods: We retrospectivly reviewed 526 consecutive patients with epithelial MPM who were surgically explored at our institution since 1988 with intent to perform EPP. Pathologic diagnoses of mesothelioma were confirmed and clinicopathologic data were recorded. Kaplan-Meyer survival from diagnosis was calculated. Those who underwent EPP were staged using BWH / DFCI (J Thorac Cardiov Surg 117:5463;1999) and AJCC (6 th Edition) criteria. Operative deaths were included in the analysis and patients received varied adjuvant regimens. Results: Of 526 patients explored for potential EPP, 53 (10%) underwent alternative pleurectomy and 55 (11%) were unresectable. The remaining 418 (79%) underwent EPP. Of these, 307 (73%) were male. Median age at diagnosis was 57.9 years (17–78). Operative mortality was 5%. Median follow-up was 16 months and 23% of observations were censored. Overall median, 1-yr, 3-yr and 5-yr survival was: 18.9 mo., 68.8%, 26.3%, and 13.9%. The table below presents Kaplan-Meyer survival by stage. Conclusions: 1) Both pathological staging systems stratify survival in this cohort, although each system is limited in that a majority of patients are classified as stage 3. 2) BWH / DFCI criteria identify more stage 1–2 patients with favorable prognosis, 164 (39%) vs 46 (11%). 3) AJCC criteria classify more patients to stage 4, 76 (18%) vs 4 (1%), but appear to identify some patients with relatively favorable prognosis. 4) Selected criteria from both systems might be combined to optimally stratify patients with epithelial MPM undergoing EPP. No significant financial relationships to disclose. [Table: see text]
Re: Christoph A. von Klot, Markus A. Kuczyk, Axel S. Merseburger. No Androgen Withdrawal Syndrome for Enzalutamide: A Report of Disease Dynamics in the Postchemotherapy Setting. Eur Urol 2014;65:258–9
Authors: Andres J Schrader, Mark G Schrader, Marcus V Cronauer
Journal: European Urology (2013)