tbuckley/cabot-search huggingface dataset:
Oral metronomic cyclophosphamide (OMC) versus megestrol acetate (MA) among patients with advanced, refractory and progressive solid tumours: A randomized phase II study
Authors: N. Penel, E. Dansin, C. Desauw, L. Mortier, S. Clisant, S. Damie, C. Fournier, M. Degardin, A. Adenis
Journal: Journal of Clinical Oncology (2008)

20603 Background: OMC has antiangiogenic properties and MA is an orexigen that may maintain the general condition in critically ill patients (pts). Anecdotal responses have been reported with both treatments. We hypothesize that both treatments may offer stable disease (SD) without any severe toxicity among such pts. Methods: This multi-centre randomized study was aimed to assess the efficacy and tolerance of both treatments. Primary endpoint was non-progression rate at 2 months (RECIST criteria). Main eligibility criteria were as follows: non-breast cancer, progressive disease before inclusion, all available effective therapies under standard care exhausted, ECOG=0–1, neither hypercalcemia nor hypoalbulminemia. Pts were randomized to receive MA 160 mg b.i.d versus OMC 50 mg b.i.d until severe toxicity or progression. The sample size calculation was based on Simon Minimax design (α=10%, β =90%, P0=5%, P1=20%). Second stage was allowed if at least 2 SD were seen among 12 pts. Results: 48 pts (25 female) were included from 9/2006 to 9/2007 (24 in each arm). TMedian age was 61 (22–84). Main locations were as follows: colorectal cancer (11 pts), Ssoft tissue sarcoma (8), lung cancer (7), unknown primaries (4) and melanoma (4). The median number of previous lines of treatment was 4 (0–10). 2/24 pts (8%) experienced SD in AM arm (1 sarcoma and 1 CRC). 4/24 pts (16%) experienced SD at 2 months in OMC arm (2 sarcomas, 1 oesophageal cancer, 1 renal cell cancer). 2 long- lasting SD (6 months +) are currently being observed in pts with sarcoma treated with OMC. No Grade 3 or 4 toxicities were notified. Treatment was discontinued in 1 case because of MA-induced deep venous thrombosis. Conclusions: OMC and MA offer SD in patients with advanced, refractory and progressive solid tumours, without any significant toxicity. This trial is ongoing in order to analyze quality of life in both arms and biological predictive factors for SD. The non-progression rate with OMC (16%) is in a same range of efficacy that was recently reported with new targeted therapy or anti-angiogenic agents administered in such pts. OMC is an inexpensive palliative treatment needing further clinical evaluations. No significant financial relationships to disclose.
Study of the relationship between RARβ2 hypermethylation and invasive esophageal squamous cell carcinoma.
Authors: Ruei-nian Li, Chun-chieh Yu, Ruei-shiang Wu, Ming-tsang Wu
Journal: Journal of Clinical Oncology (2013)

23 Background: Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer death among men in Taiwan, and the five-year survival rate is below 10%. The retinoic acid receptor beta2 (RARβ2) is frequently deleted or silenced at early stages in tumor progression. Most of RARβ2 repressions are associated with promoter hypermethylation in several epithelial carcinomas. In addition, the degree of whole genome methylation decreases as the lesion progresses from benign to invasive cells. The aim of this study is to investigate RARβ2 promoter methylation status and global methylation level in different stages of ESCC patients. Methods: We examined the methylation frequency of ESCC tissues by the method of methylation-specific PCR and pyrosequencing. The RARβ2 protein expression was determined by western blotting and cell mobility was measured by migration assay. Results: The methylation rate of RARβ2 was 21.1% (15/71) in tumor cases, but the normal control was unmethylated. The frequency of lymph nodes invasion and the frequency of tumor metastasis were 2-fold increased in RARβ2 promoter hypermethylated cases compared with normal counterparts. Furthermore, RARβ2 promoter methylation frequency was increased with 14.7% and showed significant decrease survival rate in advanced stage of ESCC patients. The level of LINE-1 methylation in ESCC tissues (mean 67%) was significantly lower than normal counterparts (mean 80%). But the level of LINE-1 methylation was not associated with tumor stage or survival rate. In vitro, ESCC cell line treated with 5-aza-dC was decreased in RARβ2 methylation level and was increased in RARβ2 protein expression. The migration ability of ESCC cell line was inhibited during demethylation of RARβ2 promoter. Conclusions: Our findings indicate that LINE-1 methylation level and RARβ2 hypermethylation could be useful for prognosis markers and invasion-migration markers in ESCC.
Eighty-three per cent of elite athletes return to preinjury sport after anterior cruciate ligament reconstruction: a systematic review with meta-analysis of return to sport rates, graft rupture rates and performance outcomes
Authors: Courtney C H Lai, Clare L Ardern, Julian A Feller, Kate E Webster
Journal: British Journal of Sports Medicine (2017)

Objectives The primary objective was to calculate the rate of return to sport (RTS) following anterior cruciate ligament (ACL) reconstruction in elite athletes. Secondary objectives were to estimate the time taken to RTS, calculate rates of ACL graft rupture, evaluate postsurgical athletic performance and identify determinants of RTS. Design Pooled RTS and graft rupture rates were calculated using random effects proportion meta-analysis. Time to RTS, performance data and determinants of RTS were synthesised descriptively. Data sources MEDLINE, EMBASE, AMED, CINAHL, AMI, PEDro, SPORTDiscus and The Cochrane Library were searched from inception to 19 January 2016. Hand searching of 10 sports medicine journals and reference checking were also performed. Eligibility criteria for selecting studies Studies were included if they reported the ratio of elite athletes who returned to their preinjury level of sport following ACL reconstruction. Twenty-four studies were included. Results The pooled RTS rate was 83% (95% CI 77% to 88%). The mean time to RTS ranged from 6 to 13 months. The pooled graft rupture rate was 5.2% (95% CI 2.8% to 8.3%). Six out of nine studies that included a noninjured control group found no significant deterioration in athletic performance following ACL reconstruction. Indicators of greater athletic skill or value to the team were associated with RTS. Summary and conclusions Eighty-three per cent of elite athletes returned to sport following ACL reconstruction, while 5.2% sustained a graft rupture. Most athletes who returned to sport performed comparably with matched, uninjured controls. This information may assist in guiding expectations of athletes and clinicians following ACL reconstruction.
Use of microRNA signature to predict patient sensitivity to dendritic cell vaccination in metastatic melanoma.
Authors: L. Ridolfi, I. Vannini, F. Fanini, L. Fiammenghi, M. Petrini, V. Ancarani, A. M. Granato, M. Guidoboni, E. Pancisi, A. Riccobon, R. Ridolfi, C. Fernandez-Cymering, S. Volinia, C. Milandri, C. M. Croce, M. Fabbri
Journal: Journal of Clinical Oncology (2011)

8591 Background: One recently developed strategy in treating patients with stage IV melanoma consists of dendritic cell (DC) vaccination. This therapy has variable results, based on patients’ immunological response to the vaccine. It has been reported that patients positive (POS) to the delayed-type hypersensitivity (DTH) cutaneous test, administered after 48h from the vaccination, are better responders to the vaccine and have longer overall survival, than patients DTH negative (NEG). At the moment there is no biological parameter that allows to preliminarly identify which patients will develop a positive DTH test, and therefore will benefit from DC vaccination. MicroRNAs (miRNAs) are short non-coding RNAs with gene regulatory functions, whose expression is de-regulated in melanoma. We asked whether a different expression of miRNAs occurs in immature (iDC) and mature dendritic cells (mDC) of metastatic melanoma patients, and whether this differential expression correlates with the response to treatment, as determined by the DTH status after vaccination. Methods: We collected iDC and mDC from 10 patients. DC maturation was obtained with a standard cocktail of cytokines (PGE2, IL-6, TNFa, IL-1b). Total RNA was extracted and hybridized with the 4.0 version of the non-coding RNA array developed at the Ohio State University, which is able to determine the expression of 476 different human miRNAs. Results: Based on our clinical database, we performed univariate analysis to determine whether miRNAs are differentially expressed in POS (n=4) vs NEG (n=6) patients, both at the iDC and at the mDC level. We identified a signature of 24 de-regulated miRNAs (10 down- and 14 up-regulated) in iDC of POS patients (better prognosis) vs NEG patients (worse prognosis), and a signature of 31 de-regulated miRNAs (9 down- and 22 up-regulated) in mDC of POS vs NEG patients. Interestingly, 5 miRNAs (miR-182, miR-150, miR-330-5p, miR-548-3p, miR-556-3p) were common to the two signatures. Conclusions: Our study indicates that miRNome aberrations at the DC level may account for a different response to treatment, and that miRNA expression in iDC and mDC can indicate which patients will benefit of a DC vaccination.
Meaningful survival after cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC): The Spanish experience.
Authors: Iria Gonzalez Maeso, Daniel E. Castellano, Begona Campos Balea, Emilio Esteban, Quionia Pérez Arnillas, M. Laura Villalobos Leon, Javier Munarriz, Gustavo Rubio, Jose David Cumplido Buron, Jose Garcia Sanchez, Almudena Martin, Jose Maria Garcia-Bueno, Ana Reyes Garcia, Begoña Perez-Valderrama, Urbano Anido Herranz, Joaquim Bellmunt
Journal: Journal of Clinical Oncology (2014)

235 Background: New emerging therapies for metastatic castration resistant prostate cancer (mCRPC), such as cabazitaxel (CBZ), have prompted the need to identify appropriate patients (pts) for each specific treatment. We describe preliminary data on the experience with CBZ in patients (pts) with mCRPC in Spain. Methods: Medical records from docetaxel-resistant mCRPC pts receiving CBZ at 15 centers in Spain were reviewed retrospectively. Baseline characteristics, PSA response, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Results: Data from 79 consecutive pts (median age 70) were reviewed: Eastern Cooperative Oncology Group (ECOG) zero to one (87.3%), Gleason score of 7 to 10 (87.1%), visceral involvement (24.1%), pain (74.7%), and radiological progression (68.4%) at CBZ initiation. Median duration of response to first-line androgen deprivation therapy was 20.8 months (mo). Most pts received less than or equal to two hormonal lines (72.2%) and only one docetaxel line (74.7%) before CBZ. Thirty-five (44.3%) pts had progressed on docetaxel. Progression less than six mo or greater than six mo after last docetaxel treatment was observed in 23 (29.1%) and 21 (26.6%) pts, respectively. New hormonal agents (abiraterone or enzalutamide) were given before CBZ in 2.5% of pts and after CBZ in 17.7%. Pts received a median of seven cycles (range 2 to 22) of CBZ. CBZ dose-reductions or -delays for any cause occurred in eight (10.1%) and 20 (25.3%) pts, respectively. Prophylactic G-CSF was given in 32 (40.5%) pts. A PSA decrease of greater than or equal to 50% and greater than or equal to 30% was reached in 41.2% and 48.6% of pts treated with CBZ. Median OS from first CBZ cycle was 16.2 [CI: 10.4;-] mo and median clinical and/or radiographic progression-free survival (rPFS) was 9.9 mo [CI: 7.4; 13.1]. Fourteen (17.7%) pts experienced at least one grade greater than or equal to 3 treatment-related AE, the most common being neutropenia (n=4), febrile neutropenia (n=2), asthenia (n=4), and diarrhoea (n=2). No grade greater than or equal to 3 peripheral neuropathy was reported. An analysis of factors predicting outcome will be presented. Conclusions: CBZ administered in real-life practice and in the adequate treatment setting in Spain is associated with meaningful PFS and OS and an acceptable safety profile. Dose delays and reductions were low. Prophylactic G-CSF use in 4 out of 10 pts may have contributed to these good results.
Treatment of bone metastases in a rural setting: The effect of Choosing Wisely.
Authors: Richard Dana Lovett
Journal: Journal of Clinical Oncology (2015)

133 Background: In 2013, the American Society of Therapeutic Radiology released its list of Choosing Wisely Initiatives. One of these initiatives was to use fraction schemes which may allow less than 10 fractions for the palliation of bony metastatic disease. Such schemes may use one or five fractions to treat an uncomplicated case of bone metastases. This project looks at a rural radiation practice, both before and after a decision was made to employ the Choosing Wisely guidelines when appropriate. Methods: This is a non-randomized, retrospective analysis of 12 months of bone metastases treatments in a single provider practice comparing the 6 months before Choosing Wisely adoption to the 6 months after. A total of 37 consecutive patients, 63 treatment sites were examined. Comparing to a standard 10 fractions of 300 cGy, fifteen treatment fractions were eliminated before adoption, 84 treatment fractions were saved after the guidelines were published. Results: Because of the bias of the practitioner, 14% of the patients received shorter fraction schedules before the Choosing Wisely adoption, 68% of patients after. As far as radiation treatment charges, $12,000 in treatments were saved before adoption, $69,000 in treatments were saved after. Besides the cost savings for the treatments, there were benefits to the patient and to the caregivers. The average patient receiving a shortened fraction schedule saved 145 miles of commuting during the course of their treatment, and saved 5 hours of commuting and treatment time. Assuming that caregivers were employed, a caregiver bringing a patient in for their treatment saved $170.00 in lost wages during the commuting and treatment time. One patient was hospitalized for her treatment and her hospital stay was reduced by the altered fractionation. No patient in the study required retreatment, the minimum follow up period was 6 months. Conclusions: Shorter fraction schemes when used as clinically appropriate do offer savings, not only to health care payers, but also to patients and to patients’ families. Consideration of Choosing Wisely Initiatives has saved patients time and expense as opposed to a similar time period before the initiative. With patients with pain from metastases, these savings are significant.
Age and peritoneal carcinomatosis in gastric cancer patients
Authors: M. J. Barros e Silva, T. F. Paiva, C. F. Benevides, L. T. Chinem, M. F. Fanelli
Journal: Journal of Clinical Oncology (2008)

15548 Background: Controversies exist as to whether the presentation and outcome of gastric cancer is different in young patients. The aim of the present study was to further investigate whether age, besides histology, impacted overall survival (OS) and peritoneal carcinomatosis (PC) in gastric cancer patients. The population was divided in two groups: younger (≤ 40 years old, n= 44) and older (≥41 years old, n=142) patients, whose clinicopathological features and outcome were compared. Methods: Medical records from 186 patients admitted from Jan. 1994 to Dec. 2004, were retrospectively reviewed. Clinicopathological characteristics, TNM stage, and follow-up were analysed. OS rates were calculated by Kaplan-Meier method and examined by the log-rank test. Patient characteristics were compared by Pearson Chi-Square and a multivariate model was designed by Cox regression method. Results: Median age was 33 (20–40) and 60 (42–91) for younger and older group respectively. Genderwise, in younger group there were 23 men (53%) against 91 men (64%) in older group. Younger patients presented higher rates of Laurén diffuse (poor histology type) carcinomas (63% vs 35%; p=0.001) than older ones, but there was no statistical significance between age groups concerning the occurrence of poor histology who developed PC (50% vs 36%; p=0.23), metastatic diseases (32% vs 25%; p = 0.6), and T3-T4 and/or N+ (43 vs 47%; p = 0.6) at diagnosis respectively. PC was more frequent in patients with poor histology against other subtypes (40% vs 13%; p= 0.0001, RR. 3.07). Among diffuse type patients, 54.8% were females (p = 0.004), regardless of age. Median survival time was similar in younger and older patients (31.5 vs 26.7 m; p = 0.59). The median OS was 27.8 months. Patients with PC showed a median survival time of 12.96 months, (13.78 m and 12 m in younger and older patients respectively p=0.02). On multivariate analysis, TNM stage in younger patients and visceral metastases in the older group were significantly associated with poor prognosis. Conclusion: The higher frequency of poor histology and peritoneal carcinomatosis observed among younger patients did not imply significant difference in overall survival when compared to the older group. A stronger association of peritoneal carcinomatosis risk with poor histology rather than age was noted. No significant financial relationships to disclose.
Monitoring acute care utilization (ACU) during adjuvant chemotherapy for early breast cancer (EBC) as a measure of quality.
Authors: Katherine Enright, Eva Grunfeld, Lingsong Yun, Rahim Moineddin, Susan Faye Dent, Andrea Eisen, Maureen E. Trudeau, Leonard Kaizer, Craig Earle, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2012)

220 Background: Serious chemotherapy associated (CA) toxicities resulting in ACU are a concern when administering adjuvant chemotherapy for EBC. Monitoring ACU during adjuvant chemotherapy may serve as a measure of quality of cancer care delivery. We undertook a population based study of ACU in patients undergoing adjuvant chemotherapy for EBC compared with controls. Methods: All EBC patients diagnosed 01/07 – 12/09 in Ontario, Canada were identified from the Ontario Cancer Registry. Patient records were linked deterministically to provincial healthcare databases. All patients received ≥1 cycle of adjuvant chemotherapy. EBC cases (n = 4,718) were matched to non-cancer controls (n = 4,718) on age and geographic location. ACUs (emergency room or hospitalizations) within 30 days of chemotherapy were identified. If the primary reason for visit was a common toxicity of chemotherapy, the visit was considered chemotherapy associated (CA). All cause and CA visits were compared between cases and controls. Logistic regression models were used to identify covariates associated with ACU. Results: ACU was significantly higher in EBC pts compared with controls for both all cause (42.1% vs. 9.1%, p&lt;.001) and CA (30.7% vs. 2.4%, p&lt;.001) visits. Fever was the most common CA toxicity (22.9% vs. 1.2%,p&lt;.001). Taxanes were significantly associated with increased ACU compared with anthracycline only (see Table). Conclusions: Serious chemotherapy associated toxicity resulting in ACU is common among EBC patients receiving chemotherapy. Interventions aimed at mitigating CA toxicity, particularly with the use of taxanes may reduce ACUs and improve quality of care. [Table: see text]
Preclinical development of a docetaxel nanocarrier to enhance prostate cancer radiosensitivity.
Authors: Gilles Crehange, Julien Boudon, Romain Boidot, Sandy Chevrier, Cecile Dalban, Alexis Loiseau, Bertrand Collin, Alexandra Oudot, Thomas Gauthier, Nadine Millot, Celine Mirjolet
Journal: Journal of Clinical Oncology (2015)

41 Background: From 30% to 50% of high risk prostate cancer patients who undergo radiation therapy (RT) will have a biochemical failure. Combining chemotherapy, such as Docetaxel (DXL), with RT can enhance its efficiency. Multidrug resistance mechanisms often limit drug efficacy by decreasing tumor cell intracellular concentration of drugs. There is interest to develop nanocarrier of DXL to maintain drug inside cancer cells by improving its efficacy. The purpose of this study was to develop a titanate-nanotube (TiONt)-DXL nanocarrier (nanohybrid) and to evaluate its in vivobiodistribution as well as its radiosensitizing efficacy in association with RT on a hormone-independent prostate cancer model. Methods: DXL molecules were grafted on TiONts using PEG-3000 molecules to generate the nanohybrid. In vitrocytotoxic activity of the nanohybrid was evaluated on PC-3 cell line using MTS assay. After intratumoral injection, biodistribution analysis was performed by SPEC-CT imaging of mice bearing subcutaneous PC-3 human prostate tumors. To evaluate the benefit of nanohybrid and RT association, tumors were irradiated using 3 fractions of 4Gy administrated after the injection of nanohybrids. Nine groups of 7 mice were used to evaluate nanohybrid and RT association efficacy : untreated, control with buffer IT injection, +/- RT, free DXL, +/- RT, TiONt +/- RT and TiONt-DXL +/- RT. Mice behavior, health status and tumor volume were monitored twice a week until tumor growth recovery. Results: Biodistribution kinetics showed that more than 70% of nanohybrids were localized into the tumor 96 hours after injection. Mice receiving nanohybrid-RT exhibited a significant tumor growth delay to reach a volume of 1,000mm 3 compared to mice receiving free DXL-RT: 73.7 days (median, [58.9-89]) vs 56 days (median, [31.5-74]) (p=0.0127). Conclusions: TiONt-DXL improves RT efficacy compared to free DXL. These results suggest that local control might be enhanced by TiONt-DXL. TiONt-DXL can be injected as a radiosensitizer in men harboring high risk localized prostate cancer with needles during prostate brachytherapy procedure.
Platelets Enhance CD4+ Lymphocyte Adhesion to Extracellular Matrix under Flow Conditions: Role of Integrins, CD40 Ligand and P-Selectin Glycoprotein Ligand-1.
Authors: Naphtali Savion, Alexey Solpov, Boris Shenkman, Grigory Brill, Yuri Vitkovsky, Alexander Koltakov, David Varon, Ilan Bank
Journal: Blood (2004)