tbuckley/cabot-search huggingface dataset:
Germ cell cancer (GCC): Long-term survival after treatment with bleomycin (B), etoposide (E), and cisplatin (P) in a large cohort.
Authors: Maria Gry Gundgaard, Jakob Lauritsen, Mette Sakso Mortensen, Mads Agerbaek, Niels Vilstrup Holm, Susanne O. Dalton, Christoffer Johansen, Gedske Daugaard
Journal: Journal of Clinical Oncology (2013)

4533 Background: In 1997 the International Germ Cell Cancer Collaborative Group presented a classification dividing patients into a good, intermediate, and poor prognostic group for metastatic GCC with 5-year survival information. However, only a minor part of these patients were treated with today’s standard treatment. We present the first nationwide and population based study of overall survival (OS) and disease specific survival (DSS) in a large cohort of GCC patients treated with BEP. Methods: A nationwide and population based clinical database covering GCC patients diagnosed 1984-2007 was constructed, including 4,683 GCC cases. Through merging with national administrative registers, information on vital status and cause of death for all patients until November 30, 2012, was obtained. Results: The 5-year OS for the whole database cohort was 96%. A total of 1,584 patients were treated with BEP (1,099 patients with primary metastatic disease, 485 patients relapsed from stage I). Until 2001, the standard treatment was 4 cycles of BEP, after 2001 patients with good prognosis had 3 cycles of BEP. Overall survival (OS) and disease specific survival (DSS) with 95% confidence intervals (95% CI) (Table), median observation time was 13.8 years. Conclusions: This cohort study showed improved OS for GCC patients across all prognostic groups since 1997, in particular regarding the poor prognostic group. The present result is based on a large number of cases established in a population based fashion, with long follow up time and unbiased information covering all cohort members including detailed clinical information and vital status of all patients. [Table: see text]
Generation of Non-Hodgkin Lymphoma Patient-Derived Xenografts and in Depth Characterization of a Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma Model
Authors: Maarja-Liisa Nairismagi, Wan Lu Pang, DaChuan Huang, Jing Tan, Jing Quan Lim, Zhimei Li, Jeslin Ha, Yurike Laurensia, Giovani Claresta Wijaya, Cedric Chuan Young Ng, Erna Gondo Santoso, Bin Tean Teh, Soo-Yong Tan, Soon Thye Lim, Choon Kiat Ong
Journal: Blood (2016)
Thrombo-embolic events (TEE) during neoadjuvant chemotherapy for muscle invasive bladder cancer.
Authors: Syed A. Hussain, Simon Gomberg, Cairine Probert, Bethan Hickerton, Richard Jackson, Robin Weston
Journal: Journal of Clinical Oncology (2017)

339 Background: Patients with muscle invasive bladder cancer receiving neo-adjuvant chemotherapy (NAC) prior to radical cystectomy or organ preservation treatment are at higher risk of thrombo-embolic events (TEE). Methods: Retrospective data were collected on patients undergoing NAC prior to radical treatment who had surveillance CT scan chest abdomen pelvis following NAC to assess for response or underwent scan following clinical presentation during NAC requiring imaging. The aim of this study was to document the incidence and characteristics of TEE during NAC prior to radical treatment. Results: Data were collected on 94 patients between January 2012 and December 2015. Median patient age was 67 (IQR: 63, 72) with 28 (30%) females. Chemotherapy received was Cisplatin and Gemcitabine in 90% of cases, Gemcitabine and Carboplatin (9%), and Cisplatin and Etoposide (1%). Performance status was 0 in 59% of cases. G3 disease was recorded in 87%, T2 or T3 in 80% and TCC in 91% of cases. 28 TEE (29.8%, 95 % CI: 20.5%, 39%) were recorded of which 22 (79%) were subclinical TEE and 6 (21%) were clinical TEE. 23 (82%) of TEE were pulmonary emboli, 2 (7%) were concurrent pulmonary emboli and deep vein thombosis, 2 (7%) were abdominal aorta thrombosis, and 1 (4%) was a deep vein thrombosis. Conclusions: Our single centre study demonstrates that the incidence of TEE during NAC prior to radical treatment for bladder cancer is high. Improved imaging techniques lead to reporting of number of sub clinical TEE of uncertain clinical significance. These findings give weight to future prospective clinical trials to investigate the role of anti-coagulation in subclinical TEE and benefit of prophylactic anti-coagulation during NAC.
The efficacy and feasibility of weekly 5-FU and cisplatin based radical concurrent chemoradiation therapy(CRT) in patients with esophageal cancer.
Authors: Joon Won Jeong, Ji Hyun Yang, Sang Mi Ro, In-Ho Kim, Sang Young Roh
Journal: Journal of Clinical Oncology (2017)

169 Background: Concurrent chemoradiotherapy(CCRT) has become a promising treatment for esophageal cancer. Mostly, however, 3 week or 4 week interval of conventional FP(5-fluorouracil plus cisplatin) regimen is adopted, which is usually associated with moderate to severe treatment-related toxicities. Studies about weekly regimen of FP CCRT are little known, thus we studied the efficaty, tolerability and toxicities of weekly FP CCRT regimen. Methods: From February 2010 to august 2015, Patients staging from I to III esophageal cancer(according to AJCC 7 th edition) were enrolled, who were received radiation therapy with dose of from 50.4Gy to 60Gy(5 days/week) and 5-FU 1000mg/BSA with cisplatin 30mg/BSA weekly. Results: From February 2010 to august 2015, 50 patients: male/female 47/3, median age 71.5 (47-78), all of 50 patients was squamous carcinoma, well/moderately differentiated carcinoma 1/18. 45 patients completed CRT without dose reduction, 9 patients received less than 6 cycles of chemotherapy, 4 patients received less than 50.4Gy of radiotherapy. Major toxicities of grade 3 or less were as follows: neutropenia 52%, thrombocytopenia 21%, nausea &amp; vomiting 10%, fatigue 10%, anemia 5%. Toxicities over grade 4 was seen only in 1 patient. 15 patients showed complete response. The median overall survival was 10.67 months(4-48). The median disease-free survival was 16.9 months. Conclusions: Weekly regimen of concurrent CRT with 5-FU and cisplatin resulted in less toxicities over grade 3. Although, this regimen still showed non-inferiority to previous conventional 4 week-interval FP CCRT regimens in terms of PFS and OS. In this study, 82% of our patients had completed CCRT without any interruption. Hence, our results suggest that CRT with weekly 5-FU and cisplatin as definitive treatment for esophageal cancer could be a tolerable regimen.
Feasigility study using tablet PC for assessment of quality of life and risk factors of breast cancer survivors.
Authors: Su-Jin Koh, Yunsuk Choi, Chung Reen Kim, Kim Ju Hee
Journal: Journal of Clinical Oncology (2017)

81 Background: The aim was to assess the feasibility of using tablet PC for assessment of risk of breast cancer recurrence and primary cancer, physical and psychological effect of breast cancer and treatment, health promotion at first visit among breast cancer survivors. Methods: The prospective study was carried out in the survivorship clinic, university teaching and tertiary referral hospital. After clearance from the Institutional Review Board, 40 breast cancer patients first visiting survival clinic received surgical treatment and adjuvant chemotherapy were included in the study after informed written consent, irrespective of the age and stage of disease. The patients were answered as per quality of life, physical function and activity, pain, fatigue, anxiety and depression, distress by using tablet PC. We evaluated the information of education, marriage, job, economic status and health, knowledge about management of cancer survivors, feasibility (difficulty, simplicity, necessity, comfort, satisfaction, recommendation) of using tablet PC and difficulty of the questionnaire in understanding, psychological, social and documenting aspect. Results: Most of patients using tablet PC agree with easy (85.7%), simplicity (75.4%), necessity (75.5%), comfort (72.1%), satisfaction (83.9%), recommendation to others (77.8%). Age over 60 years (83% vs 96%, p=0.037), general health status (r=0.491, p=0.001) affect to the difficulty of using tablet PC. And age, knowledge, education, general health status affect to the understanding of questionnaire. In multivariation analysis, educational status (elementary school (β=-0.312, p= 0.016), middle school (β=-0.452, p=0.001) and general health status (β=-0.344, p=0.010) affect to the understanding of questionnaire. Conclusions: We can use tablet PC in outpatient cancer surviors clinic effectively. But we need careful evaluation for who are not good in general health status.
Phase II chemoprevention trial: Anastrozole in DCIS and early invasive hormone-receptor (HR) positive breast cancer in postmenopausal women.
Authors: Richard Huynh, Rita S. Mehta
Journal: Journal of Clinical Oncology (2013)

e11562 Background: Anastrozole, an aromatase inhibitor, decreases estrogen synthesis and is therefore, an effective treatment of (HR) positive breast cancer. We hypothesized that a short course of anastrozole can decrease levels of Ki-67, a surrogate measure of chemoprevention (the primary endpoint), and there may be correlation in Ki-67 reduction and decreased size of tumor on MRI (the secondary endpoint). Methods: In a single group phase II trial, 42 postmenopausal women with HR positive DCIS or early invasive breast cancer following diagnostic biopsy were enrolled. Patients were given 1 mg anastrozole for 2-4 weeks. Patients had an MRI before and after anastrozole, and then underwent surgery for measurement of change in Ki-67. The specimens were histologically graded on Ki-67, estrogen receptor (ER), progesterone receptor (PR), and Nottingham grade to compare pre and post-therapeutic effects of anastrozole. The two-sided Wilcoxon signed-rank test and Fisher’s exact test were utilized to analyze the data. Spearman correlation coefficients were obtained to assess the correlation between Ki-67 and MRI. Results: 34 patients were eligible. 15 out of 23 patients (65.2%) had decreased Ki-67, 5 (21.7%) had no change and 3 (13.0%) had increased Ki-67 levels. On average, there was a significant decrease in Ki-67 level of 4.9 from baseline (95% CI 1.8, 8.0; p-value=0.004). There was a significant decrease in grade of 0.3 (0.10, 0.49; p-value=0.016). Out of 34 patients, 5 patients (14.7%) showed a pathological complete response. In terms of HR, on average, there was a significant decrease in PR of 34.5 (8.98, 60.2; p-value=0.021). However, there was no significant change in ER (p-value=0.96). Among the 12 patients who had both Ki-67 and tumor size data available, there was low correlation between the change of Ki-67 level from baseline and the change of tumor size determined by MRI (R=0. 34). Conclusions: Anastrozole, as preoperative therapy for 2-4 weeks was effective in reducing Ki-67 in early invasive HR positive breast cancer. Thus the study met its primary endpoint, and therefore supports chemo preventive effects of aromatase inhibitors as shown in large chemoprevention trials. Clinical trial information: NCT00256217.
Microfluidic-enhanced 3D bioprinting of aligned myoblast-laden hydrogels leads to functionally organized myofibers in vitro and in vivo
Authors: Marco Costantini, Stefano Testa, Pamela Mozetic, Andrea Barbetta, Claudia Fuoco, Ersilia Fornetti, Francesco Tamiro, Sergio Bernardini, Jakub Jaroszewicz, Wojciech Święszkowski, Marcella Trombetta, Luisa Castagnoli, Dror Seliktar, Piotr Garstecki, Gianni Cesareni, Stefano Cannata, Alberto Rainer, Cesare Gargioli
Journal: Biomaterials (2017)

We present a new strategy for the fabrication of artificial skeletal muscle tissue with functional morphologies based on an innovative 3D bioprinting approach. The methodology is based on a microfluidic printing head coupled to a co-axial needle extruder for high-resolution 3D bioprinting of hydrogel fibers laden with muscle precursor cells (C2C12). To promote myogenic differentiation, we formulated a tailored bioink with a photocurable semi-synthetic biopolymer (PEG-Fibrinogen) encapsulating cells into 3D constructs composed of aligned hydrogel fibers. After 3-5 days of culture, the encapsulated myoblasts started migrating and fusing, forming multinucleated myotubes within the 3D bioprinted fibers. The obtained myotubes showed high degree of alignment along the direction of hydrogel fiber deposition, further revealing maturation, sarcomerogenesis, and functionality. Following subcutaneous implantation in the back of immunocompromised mice, bioprinted constructs generated organized artificial muscle tissue in vivo. Finally, we demonstrate that our microfluidic printing head allows to design three dimensional multi-cellular assemblies with an exquisite compartmentalization of the encapsulated cells. Our results demonstrate an enhanced myogenic differentiation with the formation of parallel aligned long-range myotubes. The approach that we report here represents a robust and valid candidate for the fabrication of macroscopic artificial muscle to scale up skeletal muscle tissue engineering for human clinical application.
The effect of deprivation on uptake and outcomes in a population-based FOBt colorectal cancer screening program.
Authors: David Mansouri, Donald C. Mcmillan, Emilia M Crighton, Paul G Horgan
Journal: Journal of Clinical Oncology (2012)

3599 Background: Population-based FOBt colorectal cancer screening has been shown to reduce cancer specific mortality and is used across the UK. Despite evidence that socioeconomic deprivation is associated with increased incidence of colorectal cancer, uptake of screening may be lower in those who are more deprived. The aim of this study was to assess the impact of deprivation on the screening process. Methods: A prospectively maintained database, encompassing the first screening round in a single geographical area, was analysed with deprivation categories calculated from the Scottish Index of Multiple Deprivation 2009. Results: Overall, 395,698 individuals were invited to screening, 204,812(52%) participated and 6,094(3%) tested positive. 32% of screened individuals were in the most deprived quintile. Of the positive tests, 5,457(95%) agreed to be pre-assessed for colonoscopy. 839(16%) did not proceed to colonoscopy following pre-assessment. Of the 4,618 that attended for colonoscopy, cancer was detected in 7%. Colonoscopy results were not recorded in 1,035(22%) cases. Lower uptake of screening was seen in males, those that were younger and those who were more deprived (p&lt;0.001). Higher levels of deprivation were also associated with not proceeding to colonoscopy following pre-assessment (p&lt;0.001). Higher positivity rates were seen in males, those that were older and more deprived (p&lt;0.001). Despite higher positivity rates in the more deprived individuals (4% most deprived vs 2% least deprived, p&lt;0.001), the positive predictive value of detecting cancer in those attending for colonoscopy was lower in those who were more deprived (6% most deprived vs 8% least deprived, p=0.040). Conclusions: Socioeconomic deprivation has a significant effect throughout the FOBt screening process. Individuals who are more deprived are less likely to participate in screening, less likely to complete the screening process and less likely to have cancer identified as a result of a positive test. This study adds further weight to existing evidence that individuals who are more deprived are less likely to engage in population-based FOBt colorectal cancer screening. Novel strategies to improve this are required.
Gemcitabine and platinum (GC) chemotherapy alone or with a taxane (GC-T) as first-line therapy for urothelial cancer (UC): A meta-analysis.
Authors: Patrizia Giannatempo, Gregory Russell Pond, Guru Sonpavde, Daniele Raggi, Matt D. Galsky, Gurudatta Naik, Nicola Nicolai, Roberto Salvioni, Giuseppe Procopio, Filippo G. De Braud, Andrea Necchi
Journal: Journal of Clinical Oncology (2015)

e15526 Background: The impact of adding T to GC as first-line therapy for metastatic UC needs to be clarified. We aimed to address this question through a meta-analysis of efficacy and safety results. Methods: PubMed, EMBASE, and ASCO abstracts were searched for studies including GC +/- T in the first-line setting. We pooled trial level data including the median, proportions and confidence intervals on PFS, OS, and adverse effects. Descriptive statistics were used to summarize information across trials, and grouped by whether they contained T (docetaxel or paclitaxel) and by platinum (CBDCA or CDDP). Uni- and multivariable regression models evaluated the prognostic role of T or platinum type, after adjusting for each other, performance status (PS), and visceral disease. Data were weighted by the logarithm of the trial sample size. Results: 31 arms of trials including 2057 patients were selected (7 with T [n = 617], 15 with CBDCA [n = 623] and 16 CDDP [n = 1434]). Median OS was univariably significantly (p = 0.029) different between trials with T and those without T. Across trials, the median ‘median OS’ amongst trials containing T was 15.5 months (mo), compared with 12.5 mo in trials which did not. The % of pts with neuropathy (p = 0.025) and with neutropenic fever (p = 0.033) were also statistically significantly higher in T arms. Median of median OS was also statistically significantly superior (p = 0.041) in trials with CDDP compared to CBDCA (13.9 vs. 10.3 mo). Additionally, the rate of G3 pulmonary side effects was significantly higher in the CBDCA group (p = 0.039) while GCSF use was more frequent with CDDP (p = 0.042). Multivariably, visceral disease and PS were significantly associated with OS, while the addition of T trended to significantly better OS (p = 0.092), and platinum type was not statistically significant. The CBDCA group had a significantly higher rate of febrile neutropenia than the CDDP group (p = 0.035). Conclusions: In this meta-analysis, adding T to GC significantly extended OS on univariable analysis and trended towards improved OS on multivariable analysis. The evaluation of a more potent and tolerable tubulin inhibitor in combination with GC in a well-powered trial may be considered.
Development and validation of a Clinical Index of Severe Febrile Neutropenia: A prospective multicenter study.
Authors: Juan Virizuela Echaburu, Ana Blasco, Jeronimo Martinez, Carme Font, Maite Antonio Rebollo, Merce Biosca, Avinash Ramchandani, Jorge Hernando-Cubero, Eva Martinez de Castro, Javier Espinosa, Carmen Beato, Isabel Aragon Manrique, Francisco Javier García Navalón, Ismael Ghanem Canete, Elena Sevillano, Aránzazu Manzano, Marcelo Garrido, Eduardo Castanon, Paula Jiménez-Fonseca, Alberto Carmona Bayonas
Journal: Journal of Clinical Oncology (2015)

9617 Background: To develop and validate a prognostic score for serious neutropenic events based on characteristics available prior to starting chemotherapy Methods: FINITE is a prospective, multicenter study to assess prognostic factors and patterns of care in adult cancer patients with seemingly stable febrile neutropenia. For this analysis, we used only those clinical variables that are routinely available on Day 1 of chemotherapy in all solid tumor patients. The main outcome measure was occurrence of serious complications. A logistic regression with Penalized Maximum Likelihood Estimations (PMLE) was applied; to build an additive score, estimates were rounded as integers. To validate the model, the bootstrap bias-corrected c-index was calculated as a measure of prediction performance. A separate dataset with 216 patients was used for external validation. Results: We enrolled 1238 patients from 25 centers. The primary end point (serious complications) ensued in 161 patients (13%; 95% CI, 11.1%-14.9%) and 21 patients died (1.7%; 95% CI, 1.1%-2.6%). We developed a Clinical Index of Severe Febrile Neutropenia(CISFN) with six baseline explanatory covariates associated with serious complications: Eastern Cooperative Oncology Group Performance Status ≥ 2 (2 points), chronic obstructive pulmonary disease (1 point), chronic cardiovascular disease (1 point), protein-energy malnutrition (1 point), chronic corticoids (1 point), and inoperable locally advanced or metastatic cancer (1 point). We integrated these predictors into a score from 0 to 7, which classifies patients into three risk groups: low (0 points), intermediate (1-2 points), and high risk ( ≥ 3 points). Complications rates were 4.1% in low, 8.7% in intermediate, and 38% in high risk groups (p < 0.001). Mortality within each class was 0.2%, 1.4%, and 4.9%, respectively (p < 0.001). This model was well calibrated (Hosmer-Lemeshow test, p > 0.1) and resulted in an optimism-corrected c-index of 0.762 (95% CI, 0.759-0.763). The validation in a separate dataset yielded a c-index of 0.745 (95% CI, 0.665-0.825). Conclusions: This study identified predictive factors for serious neutropenic events with potential implications for G-CSF prophylaxis.
Recombinant human activated FVII as prophylaxis in surgical treatment of cancer patient with acquired hemophilia A.
Authors: Giacinto La Verde, Antonella Ferrari, Vincenzo Ziparo, Virginia Naso, Maria Paola Bianchi, Giusy Antolino, Francesca Saltarelli, Bruno Monarca, Federica Resci, Daniela De Benedittis, Alessandro Moscetti
Journal: Journal of Clinical Oncology (2012)

e17006 Background: Acquired hemophilia A is caused by the development of factor (F)VIII autoantibodies and results in more serious haemorrhagic symptoms than in congenital severe HA. About 50% of cases, not identified as idiopathic, are related to autoimmune diseases, viral infections, pregnancy and also neoplasms. To treat bleeds recombinant factor VIIa and activated prothrombin complex concentrate are equally efficacious while immunosuppression with steroids alone or combined with cytotoxic agents should be started as soon as the diagnosis is made. Methods: In February 2010 a woman of 58 years with acquired hemophilia A, previously treated in 1978 with cyclophosphamide and steroids without clinical benefits, was admitted to the Hematology Department of Sant’Andrea Hospital in Rome for a recent episode of spontaneous massive enterorrhagia. The diagnostic exams revealed a colorectal carcinoma (moderately differentiated G3) associated with papillary urothelial neoplasia with low malignant potential. A coagulation panel showed an aPTT ratio of 3.75 (normal range 0.8-1.2), INR 1.03 (normal range 0.9-1.2), fibrinogen 327 mg/dL (normal range 238-500), FVIII activity level of 3% (normal reference 50-150%) and FVIII inhibitor titer &gt; 100 Bethesda Units. Results: The patient was treated with left hemicolectomy and removal of the bladder lesion associated with chemotherapy XELOX (oxaliplatin 130 mg/sm day 1 q21, capecitabine 1000 mg/sm orally day 1-14 q21). From day -1 to day +15 post surgery, the patient was treated with intravenous recombinant human activated FVII at standard dose (NovoSeven ® , 90 mcg/kg every 4 hours). Our treatment avoided both intra and post-operative surgical bleeding complications, while not changing the titer of the inhibitor nor by normalizing the aPTT ratio. Actually the patient is in good clinical conditions with no further hemorrhagic episodes, although the FVIII inhibitor titer still remains high. Conclusions: We have described this case to emphasize that the presence of acquired hemophilia A in cancer patients, thanks to its specific prophylactic treatment, cannot be a limit in performing routine diagnostic and therapeutic procedures, especially surgical ones.