tbuckley/cabot-search huggingface dataset:
Clinical and histologic correlation of thymic epithelial tumors (TETs) in Korea
Authors: S. T. Kim, J. O. Park, J. Park, J. H. Han, J. G. Kim, Y. M. Shim, Y. S. Park, Y. H. Im, W. K. Kang, K. Park
Journal: Journal of Clinical Oncology (2005)

7278 Background: Thymic epithelial tumors (TETs), the most common tumor of the anterior mediastinum, are epithelial neoplasms of the thymus with a wide spectrum of morphologic features. Methods: We retrospectively analyzed clinical features of TET and the correlation of WHO histotype and Masaoka classification with different treatment modalities in 130 patients, from 1994 to 2003. Results: According to the Masaoka’s staging system, there were 48 patients with stageI, 26 with stageII, 15 with stage III, 28 with stage IVa, and 13 patients with stageIVb. According to the WHO histologic classification, 7 patients had type A, 19 had type AB, 17 had type B1, 36 had type B2, 31 had type B3, and 20 patients had type C. There was a significant correlation between Masaoka staging and WHO histotype (p<0.05). Most patients were asymptomatic at presentation, but 30 (24%) patients presented with paraneoplastic syndrome such as myasthenia gravis (20%), Cushing’s syndrome(2%), hemolytic anemia(2%). Thirty-one of 43 patients with WHO type A, AB and B1 thymomas achieved long-term complete remission with no evidence of tumor recurrence with primary complete resection alone. Among fifteen patients with type B2, B3 who received complete resection alone, only one patient relapsed. Of 39 patients with WHO type A, AB, B1, B2, B3 and C in stage I, II and III receiving complete resection with adyuvant radiotherapy, a 5-year overall survival rate (5YR OS) was 92%. Among 26 patients with stage III or higher, who had incomplete resection followed by adjuvant chemotherapy or radiochemotherapy, 5YR OS was 58% with median overall survival of 66 months (95% CI, 57–76 months). In 20 stage IV patients with primary chemotherapy or radiochemotherapy, a 3-year OS was 35% with median overall survival of 33.5 months (95% CI, 10–57 months). Conclusions: Predictive factors for poor survival were advanced stage, incomplete surgical removal, and the WHO histotype (type B3, C). Most patients with incomplete resection and WHO subtype B2, B3, C in stage III, IV died of progressive disease. Therefore, the role of adjuvant or neoadjuvant treatment modality in the treatment of patients with advanced disease and WHO subtype B2, B3, C should be further investigated. No significant financial relationships to disclose.
Epidemic profile of breast cancer at the Instituto Oncologico ION S.A. in Manizales in a developing country
Authors: C. R. Villegas Mejia, J. P. Cardona Arcila, T. Sanchez Villegas, J. A. Chacon Cardona
Journal: Journal of Clinical Oncology (2008)

11561 Background: Breast cancer is the first most common cancer in the US, the first cancer in the developing countries and it is the same in our area. Methods: It begins with a retrospective analysis from our cancer records and then it continues with prospective work from an influence area up to 1,000,000 people. Results: The group accrued 7,500 cancer patients from January 1995 to December 2006 with final analysis group of 888 patients; 99% female; median age 55 (range 25–93; SD 12.743); urban area 93%. Clinical symptom was mass (87%), best diagnosis method was test by themselves (84%), second neoplasia in 4% with contralateral breast cancer (62%), ductal carcinoma (90%), RE(+) 27%, RP(+) 27% and HER(+) 3% in only 10% of the patients; invasion lymph-vascular(+) 17%, MRM surgery 61.5%, conservative surgery 19%, mean resected nodes 13 and mean positive resected nodes 4, familiar first degree antecedent 10%, postmenopausal stage 62%, clinical stage zero (1%), I (3%), II (30%), III (29%), IV (6%) and inflammatory (6%), right breast 48%, CSE localization 51%, initial chemotherapy (QT) scheme FAC 39%, AC 36% CMF 21%; 12% changed initial QT because of pathological bad response in 67% and without clinical response with initial QT 26%; radiotherapy (RT) boost 12%; mean tamoxifen therapy 22 months and 14% patients received a second hormone therapy because of relapse; general complications 11%; lymphedema 7%; neoadjuvant treatment 43% with QT(98%) and adjuvant treatment 81% based of QT and RT (79%); global relapse (21%) with bone (51%), scar (31%), lung (20%), skin (16%), CNS (15%) and liver (13%) and overall survival by Kaplan-Meier at 5 years was 80% (95% CI: 57.2–92.4). Conclusions: These are the results of the breast cancer behavior in a specific area of a developing country like Colombia and the importance of a multidisciplinary work related to cancer treatment. No significant financial relationships to disclose.
Use of multiparametric MRI of prostate in active surveillance cohort of patients with localized prostate cancer in large urology group setting.
Authors: Richard Kronhaus, Dimitios Telonis, Christopher Michael Pieczonka, Howard Williams, David Albala, Vladimir Mouraviev, Scott Buckingham
Journal: Journal of Clinical Oncology (2015)

129 Background: The aim of this study was to determine the feasibility of using mpMRI to monitor/reclassify patients with low grade Prostate Cancer (PCa) undergoing Active Surveillance in a large urology practice. Methods: This is a retrospective study reviewing the records of 28 total patients following active surveillance (AS) protocol. All patients have been diagnosed with biopsy proven prostate cancer (PCa) and have undergone at least one mpMRI as a means of surveillance. The median total PSA of the group at time of diagnosis was 5.93 ng/ml and the mean age of the group was 64 years old. Between the 28 patients, 38 mpMRI tests were conducted, consisting of T2-weighted, diffusion weighted, and dynamic contrast enhanced MRI. Targeted ‘cognitive’ TRUS-MRI guided biopsy was used to locate progression of the PCa and help to determine whether a patient should stay on AS versus choosing more aggressive, definitive treatment. Confirmatory random biopsy was also used to determine overall sensitivity and specificity of the mpMRI conducted for suspicious regions of interest (ROI). Results: The sensitivity and specificity for the group was 65% and 92% respectively. The positive predictive value for the group was 94% while the negative predictive value was 55%. mpMRI was able to detect all clinically significant cancers except in one case. It did not detect some small size lesions (≤5.5mm) of Gleason score 6 that did not have a relevant clinical value. In five of the 28 cases (18%), patients fit the criteria for reclassification (Gleason ≥7, ≥ 3 new positive cores) out of the AS group. Four of these five patients exhibited clear progression of PCa on mpMRI and elected for more aggressive definitive treatment . The progression of cancer in the fifth patient was not seen on mpMRI but only after biopsy. This patient elected to stay in AS because of his advanced age. Conclusions: Despite the limitation of small sample size, mpMRI can be used as an effective diagnostic tool in the AS cohort of a community practice. It can facilitate early detection and progression of suspicious lesion(s) towards clinically significant PCa, thus triggering the start of more aggressive treatment.
Thymidilate synthase gene copy number as predictive marker of capecitabine efficacy in patients with breast cancer.
Authors: R. Audet, R. Duchnowska, K. Adamowicz, J. Zok, W. Rogowski, M. M. Litwiniuk, S. Debska, M. Jaworska, M. Foszczynska-Kloda, M. Kulma-Kreft, K. Zabkowska, C. Shen, S. Edgerton, K. V. Nielsen, A. D. Thor, J. C. N. Chang, K. Miller, J. Jassem, G. W. Sledge, B. Leyland-Jones
Journal: Journal of Clinical Oncology (2011)

10629 Background: Expression of key enzymes of the thymidylate synthase pathway may affect the efficacy of 5-FU and the pro-drug capecitabine (C). The gene copy number of thymidylate synthase (TS), thymidine phosphorylase (TP), and dihydrofolate reductase (DHFR) (high vs low defined by the median for each) was assessed and correlated with time-to progression (TTP) and progression-free survival (PFS). Methods: Adult female patients with pathologically confirmed breast cancer and locally advanced or metastatic disease were treated with C 1000 mg/m2 BID days 1-14 of a 21-day cycle. Human epidermal growth factor receptor 2 (HER2) and estrogen receptor (ER) expression was assessed immunohistochemically. Custom made TS, TP and DHFR FISH probes (Dako, Glostrup, Denmark) along with centromeric reference probes were used to evaluate gene copy number and gene to reference ratios in at least 60 morphologically intact non-overlapping nuclei. Markers dichotomized as high/low by the median were correlated with TTP and PFS using Cox proportional hazard models in 75, 65 and 25 patients for TYMS, TYMP and DHFR probes respectively. Results: In the overall patients population, higher TS gene copy number per cell was significantly associated with both decreased TTP (HR 1.76, 95% CI 1.07 to 2.90, p=0.026) and PFS (HR 1.86, 95% CI 1.14 to 3.04, p=0.036). 2. Higher TS gene copy number was significantly associated with a decrease in TTP (HR 1.96, 95% CI 1.09 to 3.45, p=0.025) and PFS (HR 2.07, 95% CI 1.18 to 3.65, p=0.011) in HER2 negative patients but not in HER2 positive patients (HR 1.42 and HR 1.42). 3. Higher TS gene copy number was also significantly associated with a decrease in TTP (HR 2.46, 95% CI 1.16 to 5.19, p=0.019) and PFS (HR 2.74, 95% CI 1.34 to 5.58, p=0.005) in ER positive patients but not in ER negative patients (HR 0.81 and HR 0.81). 4. TP and DHFR gene copy number were not significantly associated with clinical outcome. Conclusions: High TS gene copy number appears to be a predictor of poor outcome in ER positive, Her2 negative patients. With further refinement, TS gene copy number, assessed by FISH, may prove to be a useful and easily accessible marker for C sensitivity in human breast cancer and warrants further investigation.
Evaluation of the incidence of rare diseases: difficulties and uncertainties, the example of chronic thromboembolic pulmonary hypertension
Authors: Gérald Simonneau, Marius M. Hoeper
Journal: European Respiratory Journal (2017)

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare form of pulmonary hypertension, classified as group 4 in the present clinical classification [1, 2]. CTEPH is generally considered a late complication of one or multiple episodes of acute pulmonary embolism that have not resolved despite at least 3 months of therapeutic anticoagulation. Haemodynamically, CTEPH is characterised by a mean pulmonary arterial pressure of at least 25 mmHg at rest, measured during right heart catheterisation. The meta-analysis by Ende-Verhaar et al. provides important information and helps guide clinical practice in CTEPH <http://ow.ly/Are8307RTPx>
Royal college welcomes government’s commitment to EU workers
Authors: Abi Rimmer
Journal: BMJ (2017)

The Royal College of Physicians has welcomed the government’s commitment, as part of its negotiations on leaving the European Union, to securing the status of EU nationals working in the UK.

Jane Dacre, president of the Royal College of Physicians, welcomed the government’s response to a report by the House of Commons Science and Technology Committee on what leaving the European Union would mean for science …
Certificate of need and use of IMRT in elderly patients with low-risk prostate cancer.
Authors: Grace L. Lu-Yao, Carl Nelson, Shunhua Shen, Yu-Hsuan Shao, Hui Li, Tina M. Mayer, Dirk Moore, Sung Kim
Journal: Journal of Clinical Oncology (2013)

204 Background: Certificate of Need (CON) laws are optional from state to state, and are meant to limit proliferation of certain unnecessary medical facilities. Theoretically, CON should limit the use of IMRT (intensity modulated radiation therapy) in the population who likely would benefit from it the least: older or debilitated men with low risk prostate cancer. We evaluated the effect of CON on IMRT use in these patients in a population-based cohort. Methods: Using the Surveillance, Epidemiology and End Results (SEER) database linked with Medicare files, we identified male residents of SEER regions who were diagnosed between 2004-07 with low- risk prostate cancer (T1, Gleason≤6, PSA&lt;10) and were either ≥70 years old or ≥65 years old with Charlson comorbidity score ≥ 2. The endpoint was percentage of newly diagnosed patients who were treated with IMRT within 12 month of cancer diagnosis. Logistic regression was used to assess the impact of CON laws on IMRT use. Results: 2,263 (33%) of the patients came from states with radiation oncology CON laws, whereas 4,622 (67%) came from non-CON states. IMRT was performed on 28% of CON patients versus 24% of non-CON patients. Logistic regression analysis using two sided p-values revealed that IMRT is actually utilized more often in CON states than in non-CON states, with an odds ratio of 1.23 (95% CI 1.10-1.39, p&lt;0.001). Conclusions: CON laws do not effectively limit use of IMRT in older or debilitated patients with low risk prostate cancer.
Patient Quality of Life (QOL) In Nonsplenectomized Immune Thrombocytopenia (ITP) Patients Receiving Romiplostim or Medical Standard of Care (SOC)
Authors: Mathias J. Rummel, David J. Kuter, Romeo Mandanas, Aristoteles Giagounidis, Xuena Wang, Susan D. Mathias, Robert Deuson
Journal: Blood (2010)
A phase II trial of the histone deacetylase inhibitor belinostat (PXD101) in patients with platinum resistant epithelial ovarian tumors and micropapillary/borderline (LMP) ovarian tumors. A PMH phase II consortium trial
Authors: H. Mackay, H. W. Hirte, A. Covens, K. MacAlpine, L. Wang, M. S. Tsao, J. Pan, J. A. Zwiebel, A. M. Oza
Journal: Journal of Clinical Oncology (2008)

5518 Background: Patients with LMP ovarian tumors represent an understudied population whose tumors are intrinsically resistant to radiation and chemotherapy. Patients with platinum resistant epithelial ovarian cancer (EOC) have low response rates to conventional chemotherapy. Histone deacetylation results in loss of tumor suppressor and pro apoptotic genes in ovarian cancer cell lines. Belinostat is a pan hydroxamate, histone deacetylase inhibitor which demonstrates anti tumor activity in ovarian cancer models Methods: The aim of this phase II study is to assess the activity of belinostat in 2 patient populations: metastatic or recurrent platinum resistant (< 6 mo) EOC and LMP ovarian tumors. 3 prior lines of chemotherapy were allowed. Primary endpoints are objective response with a multinomial stopping rule, secondary endpoints include stable disease (SD) rate, survival, tolerability and assessment of molecular changes with therapy. Belinostat 1,000mg/m2/day was administered iv on days 1–5 of a 21 day cycle. Tumor response was assessed by RECIST and CA125 criteria every 2 cycles. Tumor biopsies and peripheral blood mononuclear cells (PBMCs) were obtained prior to treatment and on day 4/5 of the first treatment cycle. Results: 18 patients with EOC, median age 59.5 (range 31–78) years received a total of 50 cycles of treatment, median no. per patient 2 (range 1 to 8). 9 patients have SD, 6 progressive disease (PD), 3 are non evaluable (N/E) and 2 remain on study. 12 patients with LMP tumors received 68 cycles of treatment, median no. per patient 4 (range 1 to 13) cycles. 1 patient had a partial response (PR), 9 SD, and 2 are NE. 1 further patient had a CA125 response. 5 patients remain on study. The most frequent grade 3 adverse events (both patient groups) were bowel obstruction (4 patients), thrombosis (3), dyspnea (2), fatigue (2), lymphopenia (2), elevated ALP (2) and nausea (2). The most common adverse events any grade (% of cycles) were fatigue (80%), lymphopenia (65%), and nausea (51%). Acetylation of histones H3 and H4 was measured in tumor biopsies and PBMCs. Conclusions: Belinostat shows promising activity in LMP ovarian tumors, recruitment is ongoing. No significant financial relationships to disclose.
The effect of age on first-line sunitinib treatment in patients with renal cell carcinoma (RCC).
Authors: J. I. G. Coward, E. D. Larbi, H. S. Pandha, A. Michael
Journal: Journal of Clinical Oncology (2011)

e15096 Background: Sunitinib is a first line treatment for majority of patients with metastatic RCC. The recommended dose of 50mg often results in a spectrum of serious side effects which subsequently lead to dose reduction and may have an impact on response rates. Methods: We conducted a retrospective analysis of 62 RCC patients from single institution treated with sunitinib between September 2007-May 2010. Patients were stratified according to age groups, into ≤ 70 year old (y.o.) and > 70 y.o. to compare tolerability, response rates and median survival. Results: All patients were evaluable for toxicity, 55 patients were evaluable for response. 38 (61.2%) were ≤ 70 y.o. and 24 (38.8%) were >70y.o. 2 patients (5%) of ≤70 and 5 (20%) of > 70y.o. were non-evaluable for response due to early treatment discontinuation. The response rate was 36% in ≤70y.o. and 21% in >70 y.o., stable disease (SD) was observed in 41% ≤70 y.o. vs 47% in the older age group and progressive disease PD:22% vs 31.5% respectively. 24 (38.7%) of patients required dose reductions after the first or second cycle- 12 (33%) in ≤70 vs 11 (59%) in >70 yrs old. A small number of patients presented with PS 2 and these were started on a reduced dose of 37.5mg: 3 (8%) in ≤70y.o. and 11 (58%) > 70y.o. Toxcities were comparable in both groups however grade 3 palmar-plantar erythema (PPE) and mucositis (18% vs 1.6% and 18 vs 8% respectively) were more prevalent in the younger cohort. Grade 3 diarrhoea and fatigue were more common in older patients (10% in >70y.o vs 1.6% in ≤70y.o. and 16% vs 9.6% respectively). Median survival was 23 months for both age groups. Conclusions: Elderly patients more commonly require dose reduction due to poor performance status and toxicity profile. The objective response rate is lower with the lower dose intensity however the rate of disease stabilisation is comparable in both groups. The lower dose of Sunitinib is well tolerated in the elderly and this regimen should be considered for older patients with poor performance status.
Role of Positron Emission Tomography (PET/CT) in Primary Mediastinal Large B Cell Lymphoma (PMLBCL): Preliminary Results of an International Phase II Trial (IELSG-26 Study) Conducted On Behalf of the International Extranodal Lymphoma Study Group (IELSG), the Fondazione Italiana Linfomi (FIL) and the UK NCRI Lymphoma Group
Authors: Luca Ceriani, Emanuele Zucca, Pier Luigi Zinzani, Andrés J.M. Ferreri, Umberto Vitolo, Caterina Stelitano, Ercole Brusamolino, Maria Giuseppina Cabras, Luigi Rigacci, Monica Balzarotti, Flavia Salvi, Graziella Pinotti, Elena Porro, Erica Finolezzi, Francesco Merli, Chiara Rusconi, Silvia Montoto, Andrew Davies, Paolo Paesano, Armando Lopez-Guillermo, Franco Cavalli, Luca Giovanella, Peter Johnson, Maurizio Martelli
Journal: Blood (2012)
HER2 status in urothelial bladder cancer (UC): screening of patients eligible for a phase II randomized study of gemcitabine plus platinum salt with or without trastuzumab
Authors: A. Vieillefond, P. Beuzeboc, L. Mignot, E. Banu, F. Priou, E. Malaurie, P. Dalivoust, X. Muracciole, M. Sibony, S. Oudard
Journal: Journal of Clinical Oncology (2005)

4700 Background: The monoclonal antibody trastuzumab (Herceptin; H) is currently approved for therapeutic use in HER2 positive metastatic breast cancer. Data indicate that HER2 overexpression may be as high as 20–35% in UC, suggesting that H could be a feasible treatment option in this setting. Here, we describe the identification of patients (pts) eligible for a phase II randomized study of chemotherapy ± H in advanced or metastatic HER2 positive UC. Methods: Paraffin-embedded of tumors ± metastasis specimens from 76 pts with advanced or metastatic UC were studied immunohistochemically (IHC) with the Dako polyclonal antibody 1/1500. Correlation of HER2 expression with continous variables was tested by a Pearson’s test. Significance level was set at P<0.05, two-sided. To be included in our ongoing study, pts must either be IHC 3+ or IHC 2++ and FISH+, tested in a central laboratory. Pts will be randomized to receive gemcitabine (1000 mg/m2 day 1 and 8) and platinum salt (cisplatin 70 mg/m2 or carboplatin AUC 5, day 1, according to renal function), q3w ± H (8 mg/kg loading dose followed by 6 mg/kg q3w until disease progression). The primary endpoint is progression-free survival. Results: To date, 76 pts have been screened for HER2 status, between 02/2003 to 12/2004. Pts characteristics: median age 67 year (37–87 year), sex (F/M): 12/64. Thirty pts (39%) were eligible: 29 were IHC 3+ and one sample was IHC 2+ and FISH+. The others 46 pts were: IHC 2+ and FISH- (4 pts), IHC 1+ (6 pts) and HER2 negative (36 pts). Median HER2 quantitative expression of HER2 IHC 3+ was 100% (range 10–100%). No relationship with HER2 expression was registered for sex and age. Tumor and metastasis specimens (lymph nodes, liver) were tested for 3 pts and display the same expression. Among 30 positive pts, only 5 have currently been enrolled into the study. Conclusions: Our data demonstrate that UC is associated with a high rate (39%) of HER2 positivity, which provides the rationale for treatment with Herceptin in this disease setting. Results from this ongoing clinical trial will allow to determine HER2 eligible pts and assess the benefits of adding Herceptin to standard chemotherapy. No significant financial relationships to disclose.
The impact of a single disease site treatment facility on prostate cancer care in a community-hospital based radiation oncology practice
Authors: A. A. Konski, A. Howald, R. Starkey, P. Engstrom
Journal: Journal of Clinical Oncology (2008)

6626 Background: The purpose of this study was to evaluate the pattern of care in a community-hospital based radiation oncology practice after the opening of a referring physician-owned single disease-site specific radiation oncology facility. Methods: Hospital data for radical prostatectomy, prostate seed implants, intensity modulated radiation therapy (IMRT) treatments, and radiation oncology department profit/loss were used to evaluate changes in the pattern of care for patients with prostate cancer at a community hospital located in Central Pennsylvania (PA) between 2003 and 2007. Commonwealth of PA public claims data were used to determine the frequency of radical prostatectomy at community-hospitals in the primary service area (PSA). Comparisons of the variables of interest were made to 2003. A free- standing radiation oncology center devoted to prostate cancer care located near the community hospital was opened in 7/06. Results: Table 1 depicts the percent change when compared to 2003 of the variables of interest by fiscal year. A negative number signifies a decrease when compared to 2003 and a positive number reflects an increase when compared to 2003. Commonwealth of PA data for radical prostatectomy for 2 community hospitals in the community hospital's PSA show a similar trend for a decrease in the use of radical prostatectomy. Conclusions: Absent any clinical data that would suggest a shift in outcomes, community practice appears to have changed with the opening of a referring physician owned free-standing radiation oncology facility devoted to prostate cancer care with a 22% and 80% decrease in prostate seed implants compared to prior to the center opening. The trend towards a reduction in the use of radical prostatectomy remained unchanged. Informed consent of all treatment options for patients with prostate cancer in this market has to be questioned with the dramatic reduction in the number of prostate seed implants. Radical Prostatectomy Prostate Seed Implant IMRT Treatments Radiation Oncology Department Profits 2004 -24% 8% 177% 126% 2005 -9% 1% 196% 129% 2006 -14% -22% 147% 59% 2007 -36% -80% -17% -50% No significant financial relationships to disclose.