tbuckley/cabot-search huggingface dataset:
Reduced connexin 43 mRNA levels in human ovarian carcinoma
Authors: N. Sidell, I. R. Horowitz
Journal: Journal of Clinical Oncology (2006)

15071 Background: Cancer cells have been shown to exhibit many defects in gap junctions, which contribute to the loss of growth control and tissue homeostasis. In ovarian tissues, it is known that gap junction communication is predominantly mediated by connexin 43 (cx43) proteins. Recent studies have demonstrated that while human ovarian surface epithelial cells exhibit extensive expression of cx43, this protein is nearly absent in the vast majority of ovarian cancers. Differences in cx43 expression between normal and malignant ovarian tissue at the mRNA level has heretofore not been reported. Methods: In the present study, specimens of normal ovaries and serous adenocarcinomas were obtained at the time of laparotomy and flash frozen in liquid nitrogen. Results: Evaluation of cx43 mRNA levels by semiquantitative RT-PCR indicated significantly reduced expression in tissues obtained from ovarian adenocarcinomas compared to that from normal ovaries; the average relative levels of cx43 mRNA in tumors were less than 30% of that found in normal tissue. In one case in which tumor and adjacent normal tissue was obtained from the same patient, cx43 mRNA expression was reduced in the former to less than 10% of that found in the normal section. This data represents, to our knowledge, the first demonstration showing reduced cx43 mRNA in ovarian carcinoma. Conclusion: These findings suggest that the defect in cx43 expression in this tumor type is at the level of transcription and support the contention that its downregulation is involved in neoplastic transformation of ovarian epithelial cells. (This study was supported in part by the Vesa W. and William J. Hardman, Jr. Charitable Foundation Inc.) No significant financial relationships to disclose.
“Allow natural death” versus “Do not resuscitate”: What do patients with advanced cancer choose?
Authors: Milos Miljkovic, Dennis Omoding Emuron, Lori Rhodes, Joseph Abraham, Kenneth David Miller
Journal: Journal of Clinical Oncology (2014)

89 Background: Many patients with advanced cancer at our hospital request full resuscitative efforts at the end of life. In the first in a series of quality improvement projects to improve end-of-life (EOL) care, we assessed the knowledge and attitudes of patients towards it to determine if “Allow Natural Death” (AND) orders were more acceptable than “Do Not Resuscitate” (DNR) orders. Methods: Adult patients with advanced cancer being treated at a single community hospital were invited to participate. The first 100 consenting patients were surveyed regarding their diagnosis, prognosis, and attitudes about critical care and resuscitation. They were then presented with hypothetical scenarios in which a decision on their code status had to be made if they had 1 year, 6 months or 1 month left to live. Fifty patients were given a choice between being “full code“ and “DNR”, and 50 could choose between ”full code" and “AND”. Results: Participants were equally likely to choose either of the “no code” options in all hypothetical scenarios (p &gt; 0.54). The choice was not affected by age, sex, race, type of cancer, education, or income level. Patients who said they would want life-prolonging measures such as CPR, tracheostomies, and feeding tube placement in case of a permanent vegetative state were significantly less likely to choose “AND” than “full code” (p=0.001–0.002). A similar proportion of patients who had a living will chose “AND” and “DNR” orders instead of “full code” in all the scenarios (47–74% and 63–71%). In contrast, among patients who did not have a living will 52% chose “DNR”, while 19% opted for “AND”. More than a third (39 of 93) patients were not aware their illness was terminal. Conclusions: We hypothesized that “AND” orders may be more acceptable to patients with advanced cancer, but the wording of the “no code” order does not seem to be related to the patients’ code status decisions. The “Do not resuscitate” phrasing may be more acceptable to patients who view life-prolonging measures favorably.
Incidence of and factors associated with the burnout syndrome among Brazilian cancer physicians
Authors: A. Del Giglio, L. T. C. Tucunduva, A. P. Garcia, F. V. B. Prudente, G. Centofanti, C. M. de Souza, T. A. Monteiro, F. A. H. Vince, E. S. T. T. Samano, M. S. Gonçalves
Journal: Journal of Clinical Oncology (2005)

8143 Background: The burnout syndrome can be characterized by abnormalities in three domains: emotional exhaustion (EE), depersonalization (DP) and lack of personal realization (RP). In the medical profession, oncologists are especially prone to this syndrome. This study aims at evaluating its prevalence among cancer physicians in Brazil and correlate it to their demographic, work related variables as well as search for possible solutions to prevent it. Methods: In this prospective study we sent 3 questionnaires (Maslach burnout inventory, general and opinion questionnaires) by mail to all 645 members of the Brazilian Cancer Society. We defined burnout as proposed by Grunfeld as moderate or severe dysfunction in all three aforementioned domains. We evaluated correlations between the presence of burnout and the other variables by univariate and multiple logistic regression. Results: We received 136 responses (21%) after 10 weeks. The burnout syndrome was present at moderate or severe levels in all 3 analyzed dimensions in 15,7% (95% CI: 9,62 to 21,78%) of the surveyed physicians. For each domain, we analyzed the frequency of moderate or severe dysfunction and they were present in 55,8% for EE, 96,1% for DP and 23,4% for PR. Physical activity or having a hobby correlated significantly with lower levels of EE (p=0,008), and work restricted only to the private sector correlated with higher DP scores (p=0,021). By univariate logistic regression younger age (p = 0.002), female sex (p=0,004), number of patients seen per day (p = 0.013) and lack of family support (p=0,025) correlated significantly with burnout. By multiple logistic regression only lack of family support correlated significantly (p = 0.05) with the presence of burnout. Cancer physicians pointed out that less paper work (73,5%) and a lower patient load (72,7%) were the most important factors to prevent this syndrome. Conclusions: Burnout syndrome is frequent among brazilian cancer physicians and further studies should be conducted to try to decrease its occurrence by attempting to modify variables that may predispose physicians to it. No significant financial relationships to disclose.
Decision analysis: Excision alone versus excision plus radiation therapy for ductal carcinoma in situ.
Authors: R. S. Punglia, J. S. Wong, H. J. Burstein, J. C. Weeks
Journal: Journal of Clinical Oncology (2010)

577 Background: The benefit of adding radiation therapy (RT) after excision of noninvasive carcinoma of the breast or ductal carcinoma in situ (DCIS) is widely debated. The management of DCIS was identified as one of the highest-priority topics in the Institute of Medicine's list of areas in need of comparative effectiveness research. Methods: Using available data about the events following recurrence, we created a Markov model to compare two different treatment choices in patients with DCIS, excision alone versus excision plus RT, to uncover the magnitude of potential benefits and disadvantages of each strategy. Risk of recurrence for each arm was derived from the EORTC randomized trial. The model was run for 3 age cohorts: 45, 60, 75 years of age at diagnosis. Variables potentially able to affect model results including risks of recurrence were studied in sensitivity analyses. Results: In all age groups, RT for DCIS was associated with a slight improvement in invasive disease-free, disease-free, and overall survival (Table). However, RT decreased the chance of having both breasts intact over a patient's lifetime. On average, we calculated that RT improved invasive disease-free survival by 18.5 months for a 45-year-old woman but decreased her chance of having both breasts by 11.3%. The differences in outcomes between the treatment strategies became smaller with increasing age at diagnosis. Sensitivity analyses revealed model results to be robust over a wide range of values for key parameters. Conclusions: Our analysis reveals that while RT increases invasive disease-free, disease-free, and overall survival, the magnitude of these benefits is quite modest, especially in older women. RT also increases the likelihood of eventual mastectomy. Patient age and preferences should therefore be considered when deciding to add or forgo RT for DCIS. Age 45 years 60 years 75 years Treatment RT No RT RT No RT RT No RT Invasive disease-free survival (months) 359.1 340.6 245.1 233.4 137.5 132.0 Disease-free survival (months) 309.2 275.0 219.4 197.1 127.9 117.3 Survival (months) 430.8 426.8 280.0 277.9 149.7 149.0 Percentage with both breasts at death (%) 63.5 74.8 73.5 82.0 83.5 88.8 No significant financial relationships to disclose.
New aromatase inhibitors (AIs) as 2<sup>nd</sup>-line endocrine therapy (ET) in metastatic breast cancer (MBC): A comprehensive review of 5832 women from 14 phase III trials
Authors: P. Carlini, E. Bria, D. Giannarelli, G. Ferretti, P. Papaldo, A. Fabi, E. Ruggeri, M. Milella, E. Terzoli, F. Cognetti
Journal: Journal of Clinical Oncology (2004)

629 Background: New AIs have been developed in controlled clinical trials after tamoxifen failure in MBC. A meta-analysis of the three FDA/EMEA-approved AIs revealed that they conferred a significant survival benefit when compared with megestrol (M) (Messori, Anticancer-Drugs 2000). We performed a comprehensive review (Simes, Stat Med 1987) including phase-III trials with new AIs (2nd generation - formestane, fadrozole - and 3rd generation - letrozole, anastrozole, vorozole, exemestane) approved or not by FDA-EMEA as 2nd-line ET for MBC pts between 1996 and 2003. Methods:Published or presented trials had to met the following criteria: phase-III studies evaluating AIs as 2nd-line ET in MBC. No phase-II trials were gathered. Letters/editorials, comparative trials of 3rd-generation vs 3rd-generation AIs or given as adjuvant/neoadjuvant ET were ruled-out. Overall response rate (ORR) and time to progression (TTP) were our end-points; survival was excluded because of lack of data. For this analysis, ratios (HR and RR) and 95% confidence intervals (CI) were derived. Results: Fourteen trials were eligible (5832 pts). No significant differences were seen in the whole group of 9 trials comparing AIs vs M (3908 pts, ORR-RR 1.07, 95% CI 0.88–1.30; TTP-HR 1.00, 95% CI 0.89–1.12), in the 6 trials including non-steroidal AIs vs M (2415 pts, ORR-RR 1.10, 95% CI 0.84–1.46; TTP-HR 0.95, 95% CI 0,85–1.07), in the 3 studies comprehending steroidal AIs vs M (1493 pts, ORR-RR 1.08, 95% CI 0.61–1.94; TTP-HR 1.08, 95% CI 0.61–1.94), in 3 trials comparing 3rd generation AIs (letrozole and vorozole) vs 1st and 2nd generation AIs (aminiglutethimide and fadrazole) (1073 pts, ORR-RR 1.50, 95% CI 0.78–2.88; TTP-HR 1.18, 95% CI 0.66–2.13), and finally in 2 only studies comparing the new AI anastrozole vs the steroidal antiestrogen fulvestrant (851 pts, ORR-HR 0.86, 95% CI 0.14–1.79; TTP-HR 0.77, 95% CI 0.07–9.01). Conclusions: When all subgroups were analyzed for ORR and TTP, no significant differences were found. AIs in 2nd-line ET for MBC pts did not seem to add any significant benefit to standard comparator arm in terms of ORR and TTP. No significant financial relationships to disclose.
Antitumour Activity of the Parp Inhibitor Olaparib in Unselected Sporadic Castration-Resistant Prostate Cancer (Crpc) in the Toparp Trial
Authors: J. Mateo, E. Hall, S. Sandhu, A.G. Omlin, S. Miranda, S. Carreira, J. Goodall, A. Gillman, H. Mossop, C. Ralph, Z. Zafeiriou, R. Perez Lopez, N. Tunariu, R. Ferraldeschi, D. Nava Rodrigues, L.P. Kunju, D. Robinson, G. Attard, A. Chinnaiyan, J.S. de Bono
Journal: Annals of Oncology (2014)
BRCA mutation in Chinese population: Preliminary results from the The Hong Kong hereditary and High-Risk Breast Cancer Programme (HRBC programme)
Authors: A. Kwong, C. Wong PhD, E. Ma, J. M. Ford
Journal: Journal of Clinical Oncology (2008)

22063 Background: Inherited mutations in the cancer susceptibility genes BRCA1/2 accounts for about 70–90% of familial breast cancer based on Caucasian data. However, little is known about the frequency and spectrum of BRCA 1/2 mutations among Chinese population. Previous research suggests possible differences in the prevalence and penetrance of inherited mutations in these genes among Asians versus Caucasians. The Hong Kong Hereditary and High Risk Breast Cancer Programme (www.BreastCancerFamily.org) was established in March 2007. This is first of its kind in Hong Kong and provides clinical testing, genetic counseling and research in Chinese population. The data from this programme will be entered in The Hong Kong Hereditary Breast Cancer Family Registry (www.asiabreastregistry.com). Methods: Probands diagnosed to have breast cancer age <50, a family/personal history of breast and/or ovarian cancer, bilateral breast cancer, male breast cancer, and triple negative carcinoma were recruited. Genetic counseling was given and consent for testing were obtained. Blood and tumor samples were collected and processed for DNA and RNA extraction. The entire coding regions and flanking introns of BRCA1 and 2 were screened for germline mutations using full gene sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA). RNA analysis were done on suspicious VUS. Results: 69 Chinese Probands' blood have been sequenced and analysed. 19 (28%) deleterious mutations were identified of which 3 (16%) were novel mutations. 9 (47%) were BRCA 1 mutations and 10 (53%) were BRCA 2 mutations. 66.6% had first degree relatives with breast cancer. 8 families of probands have also been tested: a total of 26 family members, 17 of these have BRCA mutations and only 9 of them have breast cancers. 4 male family members had BRCA mutations but no breast cancer. Conclusions: Approximately 30% of the tested blood samples from clinically high risk Chinese probands carry a deleterious mutation. A high yield of BRCA mutations and a higher rate of BRCA2 mutations were found in our population. Further research on the spectrum of the mutations in Chinese will allow the tailor-making of an ethnic-based risk assessment model and preventative measures to be taken. No significant financial relationships to disclose.
Phase II clinical trial of XELOX as first line treatment for patients with unresectable or metastatic gastric cancer
Authors: R. Xu, B. Han, Y. Shi, J. Xiong, Y. Li, F. Wang, M. Qiu, W. Jiang, T. Lin, L. Zhang, Y. He
Journal: Journal of Clinical Oncology (2007)

15062 Background: The survival of advanced gastric cancer remains poor, while no chemotherapy regimen was recognized standard. Oxaliplatin and Capecitabine (Xeloda) have demonstrated promising antitumor efficacy in advanced colorectal cancer. The present study was conducted to further evaluate the efficacy and safety of XELOX (Oxaliplatin and Xeloda) regimen in gastric cancer. Methods: Patients with unresectable or metastatic gastric cancer were enrolled into this study. They all receive the XELOX regimens (Oxaliplatin 130mg/ m2 intravenously in 2 hours on day 1 followed by oral capecitabine 1000mg/ m2 twice daily for 14 days every 3 weeks).We evaluated the response every 2 cycles. Results: The median age of the total enrolled 45 patients was 55 years (range, 22–82 years), including 32 male and 13 female. They received a median of 5 cycles (range, 2–8 cycles) of XELOX. 21 of 45 patients (46.7%) achieved an objective response, 1 patient (2.2%) had completed response. 17 patients (37.8%) experienced stable disease. Median time to tumor progression (TTP) and median overall survival were not available yet due to the further follow-up needed. Most toxicity events were mild to moderate in XELOX regimen, with grade 3/4 neutropenia of 8.9 %, thrombocytopenia of 6.7%, anemia of 11.1%, hand-foot syndrome of 6.7 % and diarrhea of 6.7 %. Grade 3 neuropathy was 4.4%. The patients with advanced gastric cancer had a good tolerance to this chemotherapy. Conclusions: XELOX is a highly effective first-line treatment for unrsectable and metastatic gastric cancer. The response rates in this trial seems to be similar to those observed with FU/leucovorin/oxaliplatin combinations. XELOX is tolerable well in the treatment of advanced gastric cancer. No significant financial relationships to disclose.
Improved outcomes in HPV+ versus HPV- locally advanced head and neck squamous cell carcinoma (LAH&NSCC) when treated with cetuximab and concurrent radiation.
Authors: M. Howard, R. Slack, D. P. Hartmann, W. A. Harter, K. A. Newkirk, B. J. Davidson, F. Berkowitz, K. Steadman, D. Lockard, J. F. Deeken
Journal: Journal of Clinical Oncology (2010)

e16023 Background: Patients with LAH&NSCC caused by the human papillomavirus (HPV) have higher survival rates when treated with induction chemotherapy or concurrent cisplatin chemoradiotherapy. No previous report has shown whether these findings apply to patients treated with concurrent cetuximab (C) and radiation (XRT). Past research has found no difference in epidermal growth factor receptor (EGFR) expression in HPV+ tumors, but none have investigated differences in EGFR pathway activation by HPV status. Methods: Tumors from sequential patients treated with C and XRT were analyzed for HPV status using PCR for the E6/E7 gene sequence unique to HPV 16 or 18. Differences in overall survival (OS) and progression-free survival (PFS) were assessed by HPV status, stage, tumor (T) and nodal (N) status, primary site, and duration of XRT using the log rank test. Expression of pEGFR, pAkt, pPI3K, and pERK were measured and correlated with HPV status. Results: Between 1/07 and 11/09, 20 patients were treated with C + IMRT XRT. Primary sites included oral cavity (1), oropharynx (12), hypopharynx (1), larynx (5), and unknown (1). Six patients had stage III disease and 14 had IVa disease. Median age was 63 yrs (range 31 – 78). Median duration of XRT was 59 days (49-73). Median cycles of C was 7 (range 4 – 8). Six patients were HPV+, all were HPV16, all had oropharynx primaries, with a median age of 64 yrs. After a 19.0 mos. median follow up, 4 patients have died and 12 patients had disease progression. No correlation was found between OS or PFS and stage, T or N status, primary site, or XRT duration. For OS, 1-year and 2-year rates were 100% vs. 81% and 100% vs. 71% for HPV+ vs. HPV- tumors, respectively (p=0.11). For PFS, 1-year and 2-year rates were 100% vs. 31% and 60% vs. 31% (p=0.07). Differences in EGFR pathway activation and updated outcomes will be presented. Conclusions: Trends in improved OS and PFS by HPV status were seen in this small patient population treated with C. These findings are consistent with previous reports that HPV+ disease has a better prognosis no matter the treatment modality. Optimizing and personalizing therapy by HPV status remains the pivotal clinical research question in LAH&NSCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb
PTU-032 Differential bacterial clearance and cytokine secretion by macrophages explains localisation of Crohn's disease to the gut
Authors: B Hayee, G Sewell, F Z Rahman, S L Bloom, A M Smith, A W Segal
Journal: Gut (2010)

<h3>Introduction</h3> The clearance of <i>Escherichia coli</i> (EC) from the tissues in Crohn9s disease (CD) is grossly impaired,1 particularly at high inoculating doses of bacteria. It has not been determined whether this is specific to Gram-negative bacteria. These studies were conducted to determine whether the inflammatory response to the Gram-positive bacterium S. aureus (SA) in vivo and clearance of these bacteria is abnormal in CD. Macrophage cytokine secretion, which in CD is markedly deficient in response to stimulation with EC1, was also studied in response to SA. <h3>Methods</h3> The acute inflammatory response to SA, and clearance of <sup>32</sup>P-labelled, UV-killed SA (NCTC 6571) from a forearm injection site1 was compared over 72 h in five healthy controls (HC) and 5 patients with CD. Results were compared with historical data for EC (in the same subjects). TNF-α secretion by peripheral blood monocyte (PBMC)-derived macrophages after stimulation with SA and EC were compared in all participants, and up to n=50 for HCs and CD (using Bioassay and ELISA techniques). <h3>Results</h3> Local blood flow after inoculation of 3×10<sup>7</sup> SA was significantly lower than that observed after inoculation of 3×10<sup>7</sup> EC (p&lt;0.0001). Neither the magnitude of the inflammatory response, nor clearance of SA was different in CD compared to HCs (p=0.66). Clearance of SA in CD was more rapid than that of EC (p&lt;0.05), while in HCs, clearance of SA was slower than that of EC, but not significantly different (p=0.11). TNF-α secretion by CD macrophages was significantly reduced after stimulation with EC (p&lt;0.001). No significant differences were found in CD compared to HC after stimulation with SA. <h3>Conclusion</h3> EC is a more potent activator of acute inflammation than SA. Macrophage cytokine secretion and subsequent clearance of SA was normal in CD – a significantly different response to that seen with EC. This is likely to reflect the different composition of these organisms (particularly the presence of LPS in Gram-negative species) and could explain the restriction of CD predominantly to areas of the gastrointestinal tract containing high concentrations of Gram-negative bacteria.
Psycho-oncology via telemedicine: A model to provide services to a rural population.
Authors: Susan Krigel, Eve-Lynn Nelson, Ashley Spaulding, Hope Krebill, Melanie Leepers, Gary C. Doolittle
Journal: Journal of Clinical Oncology (2014)

236 Background: The Midwest Cancer Alliance (MCA), the outreach arm of the University of Kansas Cancer Center, developed psycho-oncology services over videoconferencing in partnership with its rural members. The collaborative goal is to address patient-identified psychosocial needs that are not currently being met in the communities. Methods: Following telemental health best practices, MCA personnel, rural site leaders, local oncology and behavioral health teams, and telemedicine staff collaborated closely to establish the service. They developed detailed protocols related to: referral and scheduling; technical training and support; paperwork; videoconferencing sessions; post-visit follow-up/documentation; and emergency management procedures. Attention was given to: confidential space; equipment to meet therapy needs; the telemedicine coordinator’s role; and completion of professional requirements (e.g., licensing, credentialing, malpractice coverage). Results: Credentialing, site implementation, and patient recruitment took longer than anticipated. To date, 15 patient visits have occurred through the psycho-oncology service across two rural sites. Worsening illness has impacted referrals as well as retention in therapy. Videoconferencing services have approximated onsite psycho-oncology strategies, with focus on evidence-based care. In general, patients have had advanced medical illness as well as significant premorbid psychosocial difficulties, such as mood disorders, substance abuse history, and relationship problems. Basic challenges to care have remained, including lack of consistent transportation. The telepsychologist’s role in relation to the rural medical team expectations is still evolving. Conclusions: The early lessons learned will continue to strengthen the psycho-oncology service as videoconferencing services expand in order to increase access. Ongoing, site-specific needs assessment remains essential, as “one size does not fit all.” Future plans include improving recruitment by coordinating referrals with distress screening. In order to provide sites with maximum flexibility, new methods of communication will be offered as they become available.