tbuckley/cabot-search huggingface dataset:
Class III β-tubulin as a predictive marker for taxane-based first-line palliative chemotherapy in recurrent or metastatic gastric cancer.
Authors: Jun-Eul Hwang, Dae-Eun Kim, Hyun-Jeong Shim, Woo Kyun Bae, Sang-Hee Cho, Ik-Joo Chung
Journal: Journal of Clinical Oncology (2013)

44 Background: Class III β tubulin (TUBB3) is a prognostic marker in various tumors and role of TUBB3 in advanced gastric cancer is not clearly defined yet. We analyzed the significance of TUBB3 expression along with ERCC1 in recurrent or metastatic gastric cancer patients receiving taxane based first-line palliative chemotherapy. Methods: We reviewed 146 patients with advanced gastric adenocarcinoma who received taxane based first-line palliative chemotherapy between 2004 and 2010 at Chonnam National University Hwasun hospital. Immunohistochemical stain of TUBB3 and ERCC1 was done in paraffin-embedded tumor tissue. We evaluated response to chemotherapy, progression-free survival (PFS), and overall survival (OS). Results: A total of 146 patients with advanced gastric cancer received docetaxel and cisplatin (n=15), or paclitaxel and cisplatin (n=131) with or without 5-fluorouracil (5-FU). The median PFS was significantly shorter for patients with TUBB3 high expression than patients with TUBB3 low expression (3.63 versus 6.67 months, p=0.001). OS was not associated with TUBB3 expression status (12.9 versus 13.1 months, p=0.769). In multivariate analysis, only TUBB3 was related to shorter PFS (HR 2.74, 95% CI 1.91-3.91, p=0.001). Patients with ERCC1 high expression showed lower response rate than patients with ERCC1 low expression (24% versus 63.2%, p=0.001), however ERCC1 showed no clinical influence on PFS and OS. Conclusions: TUBB3 is a strong predictive marker in recurrent or metastatic gastric cancer patients receiving taxane based first-line palliative chemotherapy. Clinical impact of ERCC1 is not evident in this setting.
Bevacizumab therapy in advanced non-small cell lung cancer (NSCLC): Outcomes from a community oncology network.
Authors: M. A. Neubauer, J. S. Garey, G. C. Nelson, D. A. Patt, T. H. Cartwright, J. R. Hoverman, L. T. Busby, B. D. Brooks, M. A. Sitarik, M. A. Kolodziej, R. W. Anderson, R. A. Beveridge
Journal: Journal of Clinical Oncology (2011)

e16527 Background: Bevacizumab (B) was FDA-approved in 2004 in combination with carboplatin and paclitaxel (CP) for treatment of first-line metastatic NSCLC after a phase III trial was conducted showing a median improvement in overall survival (OS) of 2 months with addition of B (10.3 vs. 12.3, HR for death, 0.79; p=0.003). The CPB regimen was added to US Oncology’s (USON) Level I NSCLC Pathway shortly thereafter; however, widespread adoption of CPB has not occurred. In this study, we analyzed OS between patients who received CP vs. CPB from the USON network. Methods: Data from USON’s electronic medical record, iKnowMed (iKM) was used to evaluate stage IV NSCLC patients from July 1, 2007 – June 30, 2009, receiving >/=1 cycle of first-line CP or CPB. Patients were excluded if they received any other B-based regimen, were enrolled in a clinical trial, or had insufficient data. Patients were followed for a minimum of 12 months. OS was calculated from first chemotherapy administration date until date of death or censored for last date of contact with documented vital signs. Patients were stratified by age, sex, and KPS. Results: During the study timeframe, 9783 NSCLC patients were identified who received any chemotherapy regimen for any line of therapy. Of these, 1572 met defined inclusion/exclusion criteria, 1057 CP (67%), 515 CPB (33%). Sex distribution was similar between the groups (M/F 57%/43% vs. 56%/44%, CP vs. CPB, respectively). More subjects in the CP arm were >65 yo or had a KPS <80 (>65 yo: 60% vs. 52%; KPS <80: 34% vs. 24%, CP vs. CPB, respectively). Overall survival for the total population was 11.4 months (CP) vs. 16 months (CPB), p<0.0001. Estimated 1- and 2-yr OS in the CP arm was 49% and 23% vs. 61% and 35% for the CPB arm. Those most likely to benefit from the addition of B, were patients <65 yo (HR 0.52, p<0.0001) or with KPS >80 (HR 0.67, p<0.0001). Conclusions: Published study results evaluating the impact of B on OS for NSCLC demonstrate a 2-month improvement. Our results support the finding that B improves OS but that this benefit is limited to certain subgroups (<65yo and KPS >80). Further study is warranted to verify these results.
Preoperative radiation therapy with concurrent capecitabine, bevacizumab, and erlotinib for rectal adenocarcinoma: A phase I trial.
Authors: Prajnan Das, Cathy Eng, Miguel A. Rodriguez-Bigas, George J. Chang, John Michael Skibber, Dipen Maru, Mark F. Munsell, Marilyn V. Clemons, Scott Kopetz, Chris R. Garrett, Imad Shureiqi, Sunil Krishnan, Marc E. Delclos, Christopher H. Crane
Journal: Journal of Clinical Oncology (2012)

544 Background: The goal of this phase I trial was to determine the maximal tolerated dose (MTD) of concurrent capecitabine, bevacizumab and erlotinib with preoperative radiation therapy (RT) for rectal cancer, with a secondary objective of evaluating pathologic complete response (pCR). Methods: Eligibility criteria included patients with clinical stage II-III rectal adenocarcinoma within 12 cm from the anal verge. Exclusion criteria included uncontrolled hypertension, recent myocardial infarction or angina, coagulopathy, impaired renal function, and history of gastrointestinal perforation. Patients were treated in cohorts of 2, in 4 escalating dose levels (DL), using the continual reassessment method, as shown in the table. Patients underwent surgery at least 9 weeks after the last dose of bevacizumab. Results: Nineteen patients were enrolled in the study: 1 withdrew early because of insurance issues and was non-evaluable. The clinical stage was T3N0 in 3, T3N1 in 13, T3N2 in 1 and T4N0 in 1 patient. No patient had grade 4-5 acute toxicity; 1 patient had grade 3 acute toxicity (hypertension, DL 2) during or within 4 weeks after RT. The MTD was not reached; the probability of dose limiting toxicity at DL 4 was 0.15. All 18 evaluable patients underwent surgery, with low anterior resection in 7 (39%), proctectomy with coloanal anastomosis in 5 (28%), and abdominoperineal resection in 6 (33%) patients. Eight patients (44%) had pCR, and an additional 8 (44%) had ≤ 10% viable tumor in the surgical specimen. Fifteen patients (83%) had T downstaging. Three patients developed grade 3 post-operative complications (ileus, small bowel obstruction and infection). After a median follow-up of 21 months (range 9-39 months), no patient had local recurrence, but 1 patient developed distant metastasis. Conclusions: The combination of preoperative RT with concurrent capecitabine, bevacizumab and erlotinib was well tolerated. The pCR rate of 44% is promising and warrants further investigation. [Table: see text]
Analysis of truncated HER2 expression and activation in breast cancer.
Authors: S. Singh, X. Liu, T. Lee, R. Kirkland, A. Kuller, L. Ohrmund, F. Lin, M. Hanna, P. Kim, B. Ybarrondo
Journal: Journal of Clinical Oncology (2010)

1099 Background: De novo and acquired resistance to trastuzumab-based therapy is an active area of research. One of the mechanisms of resistance is expression of p95HER2 which is clinically associated with aggressive disease, poor prognosis, and lack of response to trastuzumab. Clinical studies on p95HER2 are limited due to lack of highly sensitive and specific assays to accurately measure its expression and activation. Methods: A novel technology capable of specifically detecting expression and phosphorylation of receptor tyrosine kinases (RTKs) (Prometheus proprietary COPIA assay) was used to differentially detect p95HER2 from full length HER2. Using this assay, we analyzed the expression and activation of p95HER2 as well as other major oncogenic pathways including HER1, HER2, HER3, IGF1-R, c-MET, PI3K, Shc, VEGFR, and CK in 229 frozen breast cancer tissues (stage II to IV). Expression and activation of HER2, p95HER2, and PI3K were also measured in trastuzumab-resistant and -sensitive BT474 cells. Results: Here, we report the successful profiling of HER2 and p95HER2 expression and activation in frozen primary breast cancer tissues as determined by IHC and tested in COPIA. Approximately 50% of IHC 3+ samples had activated p95HER2. The level of expression and activation of p95HER2 in the IHC 2+, 1+ and negative subsets was dramatically lower although some tissues have significant levels. All 10 markers tested revealed diverse activation of signal pathways. In our preclinical studies, trastuzumab-resistant BT474 cells showed significantly higher activation of p95HER2, and PI3K compared to sensitive BT474 cells upon trastuzumab treatment. Conclusions: The highly sensitive, specific, and quantitative p95HER2 COPIA assay allows accurate detection of HER2 and total and activated p95HER2 in small tumor samples such as fine needle aspirates or core biopsies and could select patients who are most likely to respond to tyrosine kinase inhibitors. Our COPIA assay enables detection of multiple kinases simultaneously in the same samples, which sheds some light on the mechanism of p95HER2 associated trastuzumab resistance. Future studies are warranted to measure p95HER2 expression and activation in clinical responders and non-responders to trastuzumab treatment. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Prometheus Labs Prometheus Labs
The role of miRNA-145 in esophageal adenocarcinoma.
Authors: Mathieu Francois Derouet, Michael Augustine Ko, Thomas K. Waddell, Geoffrey Liu, Gail Darling
Journal: Journal of Clinical Oncology (2013)

46 Background: Carcinoma of the esophagus has become one of the fastest growing solid tumors in the world over the past 20 years and the 6 th most common cause of death in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC) pre and post induction therapy. Out of the miRNAs discovered, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold upon induction therapy however its expression was associated with shorter disease-free survival. This unexpected result was explored. Methods: In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in the EAC cell line OE33 (OE33 miR145). After validation of the expression of miR-145, several hallmarks of cancer such as cell proliferation, resistance to apoptosis and cell adhesion were analyzed. Results: There was no difference in cell proliferation and resistance to radiation between OE33 miR145 and OE33 control. However, there was a significant difference in cell adhesion. OE33 miR145 cells reattach faster than the OE33 control (72.3% cells reattached against 40.5% cells reattached after 3h, n=3, p&lt;0.05). Furthermore, OE33 miR145 cells are able to recover better than OE33 control cells after 72 hours culture in suspension (126.5 colonies against 63.5 colonies after 5 days of culture, n=2, p&lt;0.05). Conclusions: While there was no difference between the two OE33 populations in an attached state, clear differences appeared when cells were in a detached state. Although more work is required to confirm this effect, expression of miR-145 could help EAC cells in circulation by protecting them against apoptosis and helping them to reattach faster which could in turn facilitate distant metastasis.
Factors predicting the efficacy of gefitinib in patients with advanced non-small cell lung cancer (NSCLC)
Authors: K. Kishi, S. Homma, A. Miyamoto, S. Sakamoto, N. Motoi, K. Yoshimura
Journal: Journal of Clinical Oncology (2005)

7095 Background: Gefitinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, has been demonstrated its useful tumoricidal activity in advanced NSCLC. However, the association of expression of EGFR and its downstream signaling pathways with regard to the response to gefitinib is still controversial. To identify the clinical and biological features predictive of sensitivity to gefitinib, we retrospectively analyzed the efficacy of gefitinib and performed immunohistochemical (IHC) staining. Methods: From August 2002 to October 2004, 78 patients with NSCLC received gefitinib 250 mg daily. Potential factors analyzed for the response to gefitinib included age, gender, smoking history, performance status (PS), histology, stage, prior chemotherapy, prior radiotherapy, and the presence of multiple pulmonary metastases. Tumor tissues available from 47 patients were analyzed by IHC staining for the positivity of EGFR, phosphorylated (p)-EGFR, HER2, Ki-67 as well as p-Akt and p-MAPK. Results: The overall response rate of gefitinib was 28.2%. Univariate analysis revealed that the predictors of favorable response were female (p=0.004), never-smoker (p<0.0001), good PS (p=0.004), adenocarcinoma (p=0.039) and the presence of multiple pulmonary metastases (p=0.0004). Multivariate analysis showed that never-smoking history was significantly associated with good response to gefitinib (p=0.0006). Never-smokers also had significantly prolonged survival (p<0.0001). Multivariate analysis of tumor tissues revealed that a low Ki-67 labeling index (LI), that was defined as percentage of tumor cells positive, was associated with good response to gefitinib (p=0.012). In addition, patients having Ki-67 LI less than 40 showed significantly better survival than those with Ki-67 LI greater than 40 (p=0.0001). Expression of EGFR, p-EGFR, HER2, p-Akt and p-MAPK were not associated with the favorable response to gefitinib. Conclusion: Never-smokers and low Ki-67 LI are the predictive factors for good response to gefitinib as well as prolonged survival. No significant financial relationships to disclose.
Delay to colectomy and survival for patients diagnosed with colon cancer.
Authors: Sanjay Prakash Bagaria, Michael Heckman, Nancy N. Diehl, Alexander S. Parker, Nabil Wasif
Journal: Journal of Clinical Oncology (2015)

541 Background: A long wait-time for colectomy for colon cancer should theoretically affect survival but, to date, the association between delay to colectomy and survival remains unresolved. Methods: We studied 4,692 patients who underwent colectomy for colon cancer between 1990 and 2012. Wait-time was defined as the number of days between diagnosis and colectomy. Cox regression models were used to estimate all-cause mortality across wait-time categories. Multivariable analyses were controlled for clinicopathologic variables and Charlson comorbidity index. Results: The number of patients in the wait-time group of 1-28 days was 3,950 (84.2%), 29-84 days was 681 (22.7%), and &gt;84 days was 61 (1.3%). A wait-time of 29-84 days was not associated with an increased risk of death (HR=1.13; p=0.056) when compared to a wait-time of 1-28 days. Though a wait-time &gt;84 days represented a small group, it was associated with an increased risk of death (HR=1.60; p=0.013). For patients with stage I and II disease, wait-times of 29-84 days (HR =1.44; p=0.0001) and &gt;84 days (adjusted HR=2.24; p=0.0007) were associated with an increased risk of mortality. Conclusions: A wait-time for colon cancer surgery of up to 12 weeks is likely safe for most patients. However, those suspected to have early-stage colon cancer may benefit from less of delay. These data provide a framework to address concerns over prolonged wait-times and can direct efforts for timely surgical intervention in patients with colon cancer. [Table: see text]
Views of oral antibiotics and advice seeking about acne: a qualitative study of online discussion forums
Authors: M. Santer, D. Chandler, M. Lown, N.A. Francis, I. Muller
Journal: British Journal of Dermatology (2017)

Acne vulgaris is common and can significantly impair quality of life, yet little is known about patients' understanding of acne and its treatments. Oral antibiotics are widely used for acne despite concerns about antibiotic resistance. People are increasingly turning to online discussion forums for advice, and information on these sites may influence health beliefs and treatment adherence.To explore understandings about the use of oral antibiotics for acne and advice shared among messages posted on online forums.We systematically searched for online forums and identified four where acne was frequently discussed. Discussion threads relating to oral antibiotics were analysed thematically.We extracted 136 pages of data comprising 65 discussions among 294 participants. We found a wide range of perceptions around effectiveness of antibiotics for acne and concerns about adverse effects. The delayed onset of action of antibiotics was a source of frustration and compounded dissatisfaction with healthcare providers, who were perceived by people as 'fobbing them off' with prolonged courses of ineffective treatment. Advice ranged from when to ask for or insist on referral to use of costly cleansers. Forum posts related to a wide range of severities, from 'spots' to severe acne, which may make it confusing for users to assess appropriateness of information.Online forums offer opinions that could confuse patients, or lead to early abandonment of treatments, challenging consultations and patient dissatisfaction. Users expressed frustration about the delayed onset of action of antibiotics for acne, perceptions of only temporary effectiveness and adverse effects.
Study on the deterioration of verbal memory in colon cancer patients after receiving adjuvant chemotherapy.
Authors: V. Martinez Marín, S. Lopez Santiago, J. De Castro, J. A. Cruzado, C. Belda-Iniesta, J. Cano, J. Barriuso Feijoo, M. Feliu, J. Smith, J. Feliu
Journal: Journal of Clinical Oncology (2011)

509 Background: Usually, patients treated with chemotherapy (CT) complain about memory loss. This was mainly studied on patients receiving adjuvant CT for breast cancer. However there are no data on adjuvant treatment of colon cancer (CC). The aim of this study is to investigate whether adjuvant CT induces in CC patients impaired memory, particularly the verbal one. Methods: 77 patients diagnosed with stage II-III CC who received adjuvant CT for 6 months with FOLFOX-4 were included between January 2008 and May 2010. Verbal memory was investigated pre-and post-treatment by the Test Barcelona. Peña-Casanova, (1990). Results: Data of 54 patients who completed the analysis pre-and post-treatment were collected. Population characteristics are: male (61%), mean age of 66, less than 5 years of education (58.3%), stage II/III (43/57%) treated with FOLFOX-4/Xeloda (85/15%). Analysis of verbal memory performance can be seen in the table. Conclusions: We found a clear verbal memory impairment after adjuvant CT in CC patients, although the number of words Learning decreases without reaching statistical significance. Remembering of stories is significantly deteriorated after the administration of QT, affecting the patient immediate recall of stories, even when given clues. So it is the delayed recall (after 5′). This can have a negative impact on the patient's life in tasks involving immediate or delayed recall of events. This interesting finding must be tested in larger series and placebo controlled randomized trials. [Table: see text] No significant financial relationships to disclose.
Likelihood of American medical oncologists (AMOs) to order molecular testing before prescribing first-line therapy in patients with stage IV lung adenocarcinoma (l-ACA).
Authors: M. R. Green, A. J. Wozniak, S. L. Britton, J. Willey, K. E. Lemke, B. Tiscione, T. McGee, H. J. West
Journal: Journal of Clinical Oncology (2011)

e18009 Background: In 2009 we documented plans of 258 AMOs to request immunohistochemistry, FISH, or molecular testing for specific mutations prior to prescribing first-line therapy in a patient with stage IV L-ACA and PS 1 (Green et. al. J Clin Oncol 28: a7568, 2010). In 2010, we continued to use Challenging Cases, our extensively tested, live, market-research vehicle, to quantitate plans for biomarker testing, again using a specific case scenario of a former smoker patient with stage IV L-ACA and PS 1. Following ASCO 2010, we maintained the case scenario but modified the list of testing options in light of new data on EML4-ALK at ASCO 2010. Methods: In 2009, 72% (May 09), 56% (Aug 09) and 54% (Sept 09) of participating AMOs planned “no molecular testing”, while specific EGFR mutation testing alone was planned by 4%, 15%, and 10% of AMOs, respectively. In two assessments done in April and May, 2010, (N=194) rates for “no testing” were 55% and 56%, while 25% of the AMOs at each session indicated a preference for EGFR mutation testing alone, and 14% and 6% indicated plans to request both EGFR and KRAS mutation testing. After ASC0 2010, 34% of AMOs (total N = 186) assessed still favored a “no testing” plan (36% in Sept 10; 32% in Oct 10), while 26% indicated they would request EGFR mutation testing alone, 8% EGFR and KRAS mutation testing, 13% EGFR mutation and EML4-ALK assessments, and 18% testing for all 3 variables. Results: See table. Conclusions: Over the past two years, an increasing proportion of AMOs have come to favor molecular testing prior to initiating 1st line therapy in a patient with stage IV L-ACA . Approximately 1/3 of AMOs assessed after ASCO 2010 still favor no testing. The most commonly planned test is for EGFR mutation either alone or combined with KRAS or/and EML4-ALK related studies. Testing dates and number of respondents per session Testing plans 5/09 8/09 9/09 4/10 5/10 9/10 10/10 None 72% 56% 54% 55% 56% 36% 32% EGFR mutation 4% 15% 10% 25% 25% 22% 29% EFGR and KRAS mutations N/O N/O N/O 14% 6%% 8% 8% EGFR and EML4-ALK N/O N/O N/O N/O N/O 14% 13% EGFR/KRAS mutations and EML4-ALK N/O N/O N/O N/O N/O 16% 13% Other 25% 31% 35% 6% 13% 3% 5%
The imperative to invest in science has never been greater
Authors: John M. Carethers, Shaun Coughlin, Betty Diamond, Serpil Erzurum, Linda P. Fried, J. Larry Jameson, Kenneth Kaushansky, Mary E. Klotman, Stanley Lemon, Beverly Mitchell, Paul Rothman, Charles Sawyers, Christine Seidman, Stefan Somlo
Journal: Journal of Clinical Investigation (2014)

The article "Loss of nuclear pro-IL-16 facilitates cell cycle progression in human cutaneous T cell lymphoma" is being retracted, with the agreement of the corresponding author.Several duplicated bands were recently identified in the immunoblot images in Figures 1 and3, and the authors are unable to retrieve the original source files that were used to generate these data.