bluuebunny/crossref_metadata_2025_split huggingface dataset:
Administration of chemotherapy via median cubital vein without implantable central venous access port for metastatic colorectal cancer: Port-free chemotherapy.
Authors: Yoshida Yoichiro , Aisu Naoya , Naito Masayasu , Tanimura Syu , Sasaki Takamitsu , Takeno Shinsuke , Hoshino Seiichiro , Mogi Ai , Tanaka Toshihiro , Tamura Kazuo , Yamashita Yuichi 
Published: February 2017

651 Background: Repeated venous punctures are usually required in cancer patients for application of chemotherapy. Central venous catheters and implantable port systems have substantially facilitated the problem of vascular access. Safe and easy-to-handle port systems have become an integral part of daily clinical routine in oncology. However, there are several serious complications associated with central venous ports (CV-ports). With the recent development of capecitabine plus oxaliplatin (XELOX) therapy involving oral administration of drug preparations, etc., implantation of a CV-port can be avoided. The present study was undertaken to evaluate the safety of administration of chemotherapy via median cubital vein without CV port for metastatic colorectal cancer. Methods: The study included 144 patients who received XELOX + bevacizumab (BV) therapy and XELOX therapy for metastatic colorectal cancer without implantation of a CV-port. Results: Eighty-five patients experienced vascular pain, but it was transient. The drip infusion route had to be switched to the opposite side because of vascular pain in only 1 of the 144 patients. No patients required CV-port implantation or postponement of treatment due to adverse events caused by administration of the drug via the peripheral vein. Grade 3 or higher hemotoxicity was noted in 12.5%, and grade 3 or higher nonhematological toxicity was noted in 17.4%. Conclusions: We may be able to perform port-free-chemotherapy via median cubital vein for patients with colorectal cancer. We can avoid the serious complications associated with CV-port.
Molecular classification of gastric cancers by parallel examination of multiple gene amplifications.
Authors: Minarikova Petra , Benesova Lucie , Belsanova Barbora , Tuckova Inna , Belina Frantisek , Dusek Ladislav , Zavoral Miroslav , Minarik Marek 
Published: February 2017

74 Background: Gastric cancer is characterized by heterogeneity in morphology as well as on the molecular level resulting in diverse response to anticancer therapy. The subtypes are currently recognized based on histology (Lauren classification). The aim of this work was to investigate an alternative approach for description of inherent molecular mechanisms resulting in its biological behavior. Methods: Genomic DNA was extracted from formalin-fixed paraffin-embedded (FFPE) sections from 80 patients with histologically confirmed gastric cancer. A set of 70 genes was simultaneously examined by Multiplex Ligation-dependent Probe Amplification (MLPA) technique. The obtained gene amplification patterns were processed by hierarchical data clustering and evaluated in combination with clinical patientd data by multifactorial analysis. Results: The overall success rate of DNA extraction from the gastric FFPE samples was at a level of 85%. As expected HER2, MYC, p16 and b-catenin genes were among the most frequently amplified. Both statistical approaches delivered similarities in data clustering. The resulting dendrograms revealed comparably constituted subclusters of samples. Conclusions: Presence of specific gene amplification resulting from aberrant activation of various signaling pathways indicate distinct tumor characteristics that may lead to specific tumor behavior. A correlation to monitoring parameters such as progression-free survival or overall survival is ongoing. Supported by the Czech Ministry of Health grant no. NT13640.
Efficacy and safety result of trastuzumab (T-mab) and paclitaxel for T-mab naive patients with HER2-positive previously treated advanced or recurrent gastric cancer (JFMC45-1102): Final report.
Authors: Takahashi Tsunehiro , Nishikawa Kazuhiro , Miki Akira , Noshiro Hirokazu , Yoshikawa Takaki , Nishida Yasunori , Iwasa Satoru , Miwa Hiroto , Masuishi Toshiki , Yoshida Kazuhiro , Kodera Yasuhiro , Boku Narikazu , Yamada Yasuhide , Morita Satoshi , Sasako Mitsuru , Maehara Yoshihiko , Kitajima Masaki , Sakamoto Junichi , Saji Shigetoyo , Kitagawa Yuko 
Published: February 2017

79 Background: The global, randomized, phase III ToGA study showed that the first-line treatment of trastuzumab (T-mab) combined with capecitabine and cisplatin a survival (OS) benefit for patients (pts) with HER2 positive advanced or recurrent gastric cancer. However, there is no report concerning about the efficacy and safety of T-mab containing second-line treatment for T-mab naïve pts with HER2 positive advanced or recurrent gastric cancer. Therefore, we planned a phase II study of paclitaxel plus T-mab in this setting. Methods: JFMC45-1102 is multicentre phase II study. Pts with HER2 positive (IHC3+ or IHC2+/FISH+), histologically confirmed gastric adenocarcinoma, age ≥ 20, received one or more prior chemotherapy but no prior therapy with T-mab, normal left ventricular ejection fraction (LVEF ≥ 50%) were eligible. Pts received paclitaxel (80 mg/m2 on days 1, 8, and, 15 q4w) plus T-mab (8 mg/kg for the initial dose, followed by 6 mg/kg q3w) until disease progression, unacceptable toxicity or patient’s refusal. The primary endpoint was overall response rate (ORR), and the secondary endpoints include progression free survival (PFS), time to treatment failure (TTF), OS and safety. Results: A total of 47 pts were enrolled from September 2011 to March 2012.The primary endpoint ORR was 37.0% (95%CI, 23 to 52).Complete response was observed in 1 case (2.2%).The PFS data was matured, and the median PFS was 5.09 months (95%CI, 3.79 to 6.49), TTF 5.09 months (95%CI, 3.72 to 6.49), OS 16.81 months (95%CI, 13.54 to 18.65). One patient died of lung pulmonary fibrosis during therapy. The most common grade 3-4 adverse events were leucopenia (17.4%), neutropenia (32.6%), anemia (15.2%). Conclusions: Combination chemotherapy of paclitaxel plus T-mab is generally well tolerated and showed promising activity for T-mab naïve patients with HER2 positive previously treated advanced or recurrent gastric cancer. Clinical trial information: UMIN000006223.
Positive margin length and Gleason grade of tumor focus at the margin predict for biochemical failure after radical prostatectomy in patients with pT2 prostate cancer.
Authors: Nguyen Jenny N. , Chapin Brian Francis , Prokhorova Ina N. , Wang Xuemei , Davis John W. , Troncoso Patricia 
Published: February 2017

103 Background: While three prospective trials have demonstrated benefit from adjuvant radiation (XRT) after radical prostatectomy (RP) in patients with positive surgical margins (PSM), its use varies amongst physicians. Many rely on clinical acumen to determine the optimal strategy for application of XRT post RP. We aim to determine if the length of PSM and highest Gleason grade (GG) of tumor at the PSM (hGGPSM) can be used to identify patients at greatest risk of biochemical failure (BCF) post RP. Methods: A retrospective review of all RP patients at The University of Texas MD Anderson Cancer Center from 2002 to 2010 was performed. After a single pathologist review, patients with organ confined disease (pT2), pathologic N0/Nx and a PSM were included. BCF was defined as 2 sequential PSA values of ≥0.2 or any detectable PSA prompting XRT. Patients receiving adjuvant XRT or with <12 months follow-up were excluded. Results: 205 patients met the inclusion criteria. Median PSA was 5.3 ng/mL (0.5-33) and median follow-up was 64 months (13-130). The majority were low clinical stage (cT1c: 65%), low (11%)/intermediate (82%) grade and had a single site of a PSM (90%). BCF occurred in 47 patients for a 5 yr BCF free survival (BCFFS) of 69%. PSM length was significantly associated with BCFFS (≤1mm vs >1, p=0.02). When accounting for hGGPSM, Gl 3 tumors were less likely to experience BF (5 yr BCFFS-96%) regardless of PSM length, while BCFFS for Gl >3 tumors were significantly lower dependent upon length of PSM ( ≤1mm vs >1mm, p=0.03). On multivariable analysis length of PSM (p=0.05) and hGGPSM (p=0.007) remained independent predictors of BCF (Table). Conclusions: Length of PSM and hGGPSM are independent predictors of BCF. These should be considered when evaluating patients for adjuvant XRT and in risk stratifying patients in prospective clinical trials. [Table: see text]
ARv567es as detected in circulating tumor cells: An innovative methodology for the detection of a prognostic and therapeutic biomarker.
Authors: Shah Avani Atul , Kang Zhigang , Madan Ravi Amrit , Marte Jennifer L. , Gulley James L. , Dahut William L. , Cao Liang 
Published: February 2017

112 Background: Increased androgen receptor (AR) expression and signaling is associated with the progression of prostate cancer. Constitutively active AR splice variants (ARVs) are thought to arise following castration and play a key role in progression. The most well studied variant, ARv567es, lacks portions of the ligand-binding domain, increasing expression of full-length AR and transcriptional activity of AR in human prostate cancer cell lines. Tumor-derived tissue can be difficult to obtain for molecular studies on patients (pts) with castration-resistant prostate cancer (CRPC), with circulating tumor cells (CTCs) representing a unique avenue to investigate changes at the molecular level. Methods: Forty-seven whole blood samples drawn from 36 pts with metastatic CRPC (mCRPC) were processed for CTC isolation followed by molecular characterization of cDNA using epithelial tumor markers and prostate cancer specific markers. Microfluidics devices used in this study for CTCs isolation and retrieval is a surface marker independent, label-free cell trap system developed to isolate CTCs based on cell size and deformability (Clearbridge Biomedics). The ARv567eswas detected by multiplex digital PCR System (BioMark HD, Fluidigm) and confirmed by Sanger sequencing. Results: Four out of 36 pts and 6 out of 47 samples had the ARv567es.. The ARv567esamplified from three pts was confirmed by Sanger sequencing in which the ligand binding domain of the receptor was absent. Metastatic disease on presentation was seen in three out of four pts with the ARVs. The ARVs were detected late in the disease course, with the survival after assessment being brief (49, 106, and 200 days) for three out of four pts. One patient is still at 343 days. Due to the nature of this analysis it is unclear when these ARVs developed since baselines samples were not available. Conclusions: This is the first report of the ARv567es found in CTC-enriched peripheral blood samples from CRPC pts. This methodology can also be employed to find other ARVs, which could serve as potential biomarkers in pts, allowing for more appropriate treatment selection based on tumor evolution. This noninvasive method could significantly impact the molecular characterization and potentially the treatment science of CRPC.
The effect of change in PSA velocity on overall survival (OS) in men with biochemically recurrent prostate cancer (BRPC) treated with nonhormonal agents: Combined analysis of four phase 2 trials.
Authors: Suzman Daniel L. , Zahurak Marianna , Carducci Michael Anthony , Eisenberger Mario A. , Antonarakis Emmanuel S. 
Published: February 2017

121 Background: A number of phase 2 trials in men with BRPC have assessed the impact of non-hormonal agents on PSA kinetics. We have previously demonstrated that changes in PSA kinetics are correlated with metastasis-free survival; however, it is unknown whether these changes may also correlate with overall survival (OS). Methods: We performed a combined retrospective analysis of 146 men with BRPC treated on phase 2 trials using one of four investigational drugs: lenalidomide (n=60), marimastat (n=39), ATN-224 (n=22), and imatinib (n=25). We examined factors influencing OS, including within-subject changes in PSA kinetics (PSA slope, PSA doubling time, and PSA velocity) before and 6 months after treatment initiation. Results: After a median follow up of 77 months, 47 men had died. In univariate Cox regression analysis, four factors were associated with OS: prior androgen deprivation therapy (ADT), prior local radiotherapy, baseline PSA velocity, and change in PSA velocity after therapy. In a landmark multivariable model, stratified by study, which also controlled for age and Gleason score (<7 vs ≥7): prior radiotherapy, baseline PSA velocity, and increase in PSA velocity remained independent predictors of OS (Table). Median OS for men with an increase in PSA velocity on treatment was 9.1 years vs 12.3 years for men with a decrease in PSA velocity (HR 1.95; 95%CI 1.07–3.57; P=0.03). Conclusions: This hypothesis-generating study suggests that within-subject changes in PSA velocity after initiation of non-hormonal therapy may correlate with OS in men with BRPC. If validated in prospective trials using OS as the primary endpoint, change in PSA velocity may represent a reasonable intermediate endpoint for screening new agents in these patients. [Table: see text]
The effect of image-guided radiation therapy on rectal and urinary toxicity when radiating the prostatic fossa.
Authors: Spieler Benjamin , Goldstein Jeffrey , Pail Orrin , Samueli Benzion , Saad Akram , Ben-Betzalel Guy , Ben-Nyun Maoz , Tzvang Lev , Weiss Ilana , Lawrence Yaacov Richard , Berger Raanan , Symon Zvi 
Published: February 2017

137 Background: The 2013 ASTRO/AUA consensus statement reports that most outcome data for patients with biochemical failure is based on the use of older treatment techniques. Studies reporting outcomes for patients treated with modern techniques are needed. Methods: Patients were treated using the EORTC guidelines for determining the prostate fossa volume and radiation dose was above 64 Gray. 3D conformal planning and 3D treatment techniques including IMRT and VMAT were used. Daily image guidance was introduced in 2008 using cone beam CT scan and KV/KV imaging using surgical clips as fiducial markers. Toxicity and side effects were recorded and compared to patients treated prior to introduction of image guidance. Results: The Table shows toxicity results prior to and after introduction of daily image guidance. χ2 analysis indicates significant differences for GI, GU and overall toxicity between pre-IGRT and post-IGRT patient groups. Conclusions: Our results are consistent with other reports showing that salvage radiation therapy to the prostatic fossa or prostatic fossa and pelvic lymph nodes is well tolerated with few significant acute or late complications. We noted a significant decrease in GI toxicity and in GU toxicity with the introduction of image guidance techniques. [Table: see text]
Impact of prior endocrine therapy on radiographic progression-free survival (rPFS) in patients (pts) with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC): Results from COU-AA-302.
Authors: Oudard Stephane , Kheoh Thian San , Yu Margaret K. , Smith Matthew R. , Small Eric Jay , Mulders Peter F.A. , Fizazi Karim , Rathkopf Dana E. , Saad Fred , Scher Howard I. , Bellmunt Joaquim , Taplin Mary-Ellen , Davis Ian D. , Schrijvers Dirk L. , Protheroe Andrew , Molina Arturo , Griffin Thomas W. , De Bono Johann Sebastian , Ryan Charles J. 
Published: February 2017

14 Background: Abiraterone acetate (AA), a prodrug of abiraterone, which is a selective androgen biosynthesis inhibitor, prolongs overall survival (OS) in mCRPC pts and is approved for use in this population. An exploratory analysis was conducted to determine the impact of prior endocrine therapy on clinical benefit of AA in COU-AA-302, a randomized phase 3 study of pts with chemotherapy-naive mCRPC. Methods: 1,088 pts (testosterone < 50 ng/dL; receiving continuous gonadotropin-releasing hormone [GnRH] agonist if not orchiectomized) were randomized 1:1 to AA (1 g) + prednisone (P) (5 mg BID) or placebo + P alone. rPFS and OS were co-primary end points. rPFS was defined as time to first occurrence of bone scan progression by PCWG2 criteria, progression by CT/MRI by modified RECIST 1.0 criteria, or death, whichever came first. Comparison of the treatment effect on rPFS (investigator review at 55% of OS events) was made for the subgroups above or below the median duration of prior endocrine therapy in 2 categories: either prior GnRH agonist or prior antiandrogens. Cox model was used to obtain the HR and associated 95% CI with statistical inference by log rank statistic. Results: Most pts received prior GnRH agonists and antiandrogens (Table). rPFS was significantly more favorable with AA than P irrespective of the median duration of prior GnRH agonist or antiandrogen therapy. Increased median rPFS was observed in pts with longer prior exposure to GnRH agonists or antiandrogens comparing within both AA and P treatment groups. Conclusions: As shown in this COU-AA-302 exploratory analysis, duration of prior endocrine therapy, as analyzed after the onset of mCRPC, does not appear to impact clinical benefit of AA in pts with chemotherapy-naive mCRPC. Clinical trial information: NCT00887198. [Table: see text]
AXIN2 and prostate cancer recurrence after radical prostatectomy.
Authors: Hu Brian Robin , Fairey Adrian Stuart , Yang Dongyun , Li Meng , Groshen Susan G. , Stephens Craig , Quinn David I. , Kim Philip , Virk Navneet , Wang Lina , Martin Sue Ellen , Gill Inderbir S , Goldkorn Amir 
Published: February 2017

145 Background: Sub-populations of cancer stem cells (CSC) present in prostate cancer (PCa) and other malignancies have been associated with more aggressive characteristics. We investigated whether tumor expression of genes putatively linked to the CSC phenotype is associated with PCa recurrence. Methods: Expression of mRNA from radical prostatectomy specimens in 241 patients (cases 147, control 94) was analyzed by RT-PCR. Univariate analysis and recursive partitioning measured associations between expression of 12 CSC genes and PCa recurrence. Bootstrap internal validation was used to confirm associations. External validation was performed in-silico using the Oncomine microarray data compendium, analyzing differential gene expression in relevant studies. Results: Four genes (AXIN2, p<0.001; CD44A, p=0.036; OCT 4, p=0.017; TACSTD2, p=0.008) were differentially expressed in PCa recurrence. Recursive partitioning analysis identified three genes jointly predictive of disease recurrence (AXIN2, NANOG, CTNNB1; OR 5.1 to 8.5). Bootstrap internal validation identified low AXIN2 expression as the CSC gene most predictive of PCa recurrence. In-silico external validation was performed for AXIN2, identifying one closely-matched cohort. Primary data analysis confirmed the association between low AXIN2 expression with PCa recurrence after prostatectomy (p=0.003). Additional queries of the Oncomine platform correlated low AXIN2 expression to worse disease in PCa: metastatic versus primary (six of seven studies, p=2.6x10-9 to 0.07) and locally-advanced versus low grade (four of seven studies, p= 0.007 to 0.037). Lastly, low AXIN2 expression was associated with worse disease in multiple other cancers (10 of 10 studies, p=7.7x10-6 to 0.007). Conclusions: Low AXIN2 expression was internally and externally validated as predictive of PCa recurrence after radical prostatectomy. In-silico analysis demonstrates low AXIN2 expression is associated with more aggressive disease and worse clinical outcomes in prostate and other cancer cohorts. This novel finding delineates a link between the CSC phenotype and disease prognosis, suggesting AXIN2’s role as a potential biomarker.
Impact of tertiary Gleason pattern 5 on prostate cancer aggressiveness: Lessons from a contemporary single institution radical prostatectomy series.
Authors: Koloff Zachary Benjamin , Hamstra Daniel A. , Wei John Thomas , Montgomery Jeffrey Scott , Tomlins Scott A. , Wu Angela J. , Morgan Todd Matthew , Siddiqui Javed , Paich Kellie , Chinnaiyan Arul M. , Feng Felix Yi-Chung , Weizer Alon Z. , Hollenbeck Brent K. , Kunju Lakshmi Priya , Miller David Christopher , Palapattu Ganesh S. , Mehra Rohit 
Published: February 2017

15 Background: This retrospective study was conducted to better evaluate the impact of tertiary Gleason pattern 5 (TP5) on tumor pathological features and biochemical recurrence following radical prostatectomy (RP). Methods: We retrospectively reviewed 1,965 patients who underwent RP for clinically localized prostate cancer; TP5 was reported in 159 cases (8.1%). Men with Gleason score (GS) 7 and GS 8 disease were divided into two subgroups, with and without TP5, and histopathologic features were compared. Multivariate analyses and Kaplan-Meier curves were conducted to assess the impact on TP5 on biochemical-free survival (BFS). Results: Tumors possessing GS 3 + 4 with TP5 were significantly more likely to exhibit extraprostatic extension (EPE) and have a larger tumor diameter (TD) than GS 3 + 4 alone. GS 3 + 4 with TP5 was also associated with positive surgical margins (SM), seminal vesicle involvement (SVI), and higher pre-operative PSA values, but without statistical significance. GS 4 + 3 with TP5 more commonly presented with EPE, positive SM, SVI, and greater TD and PSA than GS 4 + 3 alone, with significance. In multivariate analysis, TP5 was shown to be an independent risk factor for PSA recurrence (Table). Additionally, GS 4 + 3 with TP5 was associated with shorter time to recurrence versus GS 4 + 3 alone. Conclusions: Our results emphasize the importance of high-grade tertiary patterns and suggest that criteria for tertiary pattern reporting in prostate cancer should be standardized. In addition, further studies are needed to evaluate the role of tertiary patterns in prognostic models. [Table: see text]
Effect of a genomic classifier on adjuvant radiation recommendations after prostate cancer surgery.
Authors: Badani Ketan K. , Thompson Darby J. S. , Buerki Christine , Singh Amar 
Published: February 2017

151 Background: Clinical guidelines recommend adjuvant radiation therapy (ART) after radical prostatectomy in men with adverse pathological features. Practice patterns vary on use of ART. This prospective, multi-center study examines the effect of a genomic classifier (GC) on ART recommendations post-prostatectomy. Methods: A prospective, pre-post tumor-board–like survey was conducted to assess urologists’ treatment recommendations for ART as part of a clinical utility study; results are from a pre-specified interim analysis of 11 unique de-identified cases with adverse pathology. All case histories were based on patients treated by at least one of the urologists participating in the study. Patient age, pathological features, and preoperative prostate-specific antigen were presented to the respondents. Presentation of cases was randomized to minimize recall bias. For each case history, physician respondents first were asked to render an ART recommendation without knowledge of the GC findings (pre-GC); they were then asked to render an ART recommendation after GC findings were provided for the same cases (post-GC). Recommendations were made without knowledge of others’ responses. Results: Twelve urologists at 11 US institutions provided 132 adjuvant therapy recommendations. Pre-GC, ART was recommended in 56 (42%) cases. Thirty three percent (95% CI: 25-41%) of recommendations changed following review of GC results. Among pre-GC recommendations for ART, 39% (95% CI: 27-53%; n=22) changed to observation and among pre-GC recommendations for observation, 8% (95% CI: 3%-17%; n=5) changed to ART. Compared to observation, ART was 11.8 times (odds ratio 95% CI: 2.9 - 46.3) more likely to be recommended for cases with high risk GC scores. Adjuvant therapy recommendations were more strongly influenced by GC score (p=0.0006) than any clinical variable (all p>0.33) when both informed recommendations. Conclusions: Additional knowledge of the tumor’s genomic characteristics, as assessed by GC, results in a statistically significant and clinically meaningful change in treatment recommendations in patients indicated for adjuvant radiation therapy by current clinical guidelines.