bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of neuroendocrine phenotype with platinum chemotherapy outcomes in men with metastatic prostate cancer.
Authors: Humeniuk Michael Sandon , Gupta Rajan T , McNamara Megan Ann , Ramalingam Sundhar , Harrison Michael Roger , George Daniel J. , Wu Yuan , Healy Patrick , Armstrong Andrew J. 
Published: September 2018

e16532 Background: DNA repair defects are common in men with mCRPC, and platinum chemotherapy may have a role in selected patients. We aimed to determine whether neuroendocrine variant prostate cancer (NEPC) is associated with a greater response to platinum chemotherapy, as compared to CRPC with adenocarcinoma histology (AdenoCRPC). Methods: We conducted a retrospective cohort analysis of all patients with prostate cancer treated with platinum chemotherapy at the Duke Cancer Center between 2005-15. The primary endpoint was objective response rate (RESIST v1.1; ORR); secondary endpoints were PSA decline, progression-free (PFS) and overall survival (OS). Outcomes were compared by histologic phenotype (NEPC vs. AdenoCRPC). Results: Between 2005-2015, 73 men, including 56 with AdenoCRPC and 17 with NEPC, were treated with platinum-based chemotherapy for mCRPC. Carboplatin-docetaxel and carboplatin/cisplatin etoposide were the most common regimens. Fifteen men (21%) were M1 at diagnosis. Among NEPC patients, 3 had primary NEPC/small cell carcinoma at diagnosis, while 14 had NEPC transformation after hormonal therapy. Overall, 24% of NEPC men received prior docetaxel vs. 75% of AdenoCRPC men. Partial responses were observed in 59% in men with NEPC vs. 25% for AdenoCRPC. Primary progressive disease occurred in 24% (NEPC) vs. 48% (AdenoCRPC). PSA declines with platinum chemotherapy were more common in NEPC (median 72% decline) vs. AdenoCRPC (median 24% decline). There was no significant difference in median PFS or OS between phenotypes (NEPC PFS 5.1 mo, OS 8.5 mo; AdenoCRPC PFS 4.3 mo, OS 10.0 mo; p = NS). For second platinum chemotherapy, ORR and PFS in NEPC vs AdenoCRPC were 67% and 5.2 months vs. 14% and 4.6 months. Conclusions: Our data suggest that men with NEPC histology have a greater probability of objective response and PSA decline with platinum chemotherapy vs. men with AdenoCRPC. However, PFS and OS are similar across histologic phenotypes, indicating similar times to resistance to platinum chemotherapy. Biomarkers of platinum sensitivity are needed, and evaluation of DNA repair defects in this setting may provide a greater opportunity for precision medicine approaches to DNA damaging agents.
Prostate clinical outlook visualization for patients and clinicians considering cyberknife treatment: A personalized approach.
Authors: Park Jihwan , Rho Mi Jung , Dritschilo Anatoly , Collins Sean P. , Suy Simeng , Choi In Young , Mun Seong K. 
Published: September 2018

e16549 Background: When a patient presents with localized prostate cancer, referral for radiation oncology consultation includes a discussion of likely outcomes of therapy. Among current radiation treatments for prostate cancers, hypo-fractionated stereotactic body radiation therapy (SBRT) has gained clinical acceptance based on efficacy, short duration of treatment and potential radiobiological advantages. The prostate Clinical Outlook (PCO) visualization system was developed to provide the patient and the clinician with a tool to visualize probable treatment outcomes using institutional, patient specific data for comparing results of treatment. Methods: We calculated the prostate cancer outlooks for each prospective patient using the EPIC-26 quality of life parameters based on clinical outcomes data of 580 cyberknife SBRT treated prostate cancer patients. We applied Kaplan-Meier analysis using the ASTRO method for disease free likely outcome and the PCO nomogram to calculate parameters for quality of life. Open source R, R/Shiny, and MySQL were used to develop a modularized architecture system. Results: PCO presents patient specific risk scores in a gauge chart style and risk free probability bar plots to compare treatment data of cyberknife patients. PCO generates reports, in PDF and HTML, which consist of a comparison chart of risk free probabilities and gauge charts of risk scores. This system is now being expanded as a web-based service to patients. Conclusions: PCO visualized patient specific likely outcomes were compared to treatment data from a single department, helping the patient and the clinician to visualize likely outcomes. The PCO approach can be expanded to other specialties of oncology with the flexible, modularized architecture which can be customized by changing parameter variables for the modules.
Evaluation of microarrays for measuring cell cycle progression (CCP) gene expression.
Authors: Stone Steven , Cooperberg Matthew R. , Flake Darl D , Davis John W. , Moul Judd W. , Tward Jonathan David , Brawer Michael K. 
Published: September 2018

e16566 Background: A CCP score has been developed and validated to provide prognostic information in prostate cancer. To date, our studies have exclusively used qRT-PCR to measure CCP gene expression, which is generally considered the ‘gold-standard’ for measuring RNA expression levels. However, qRT-PCR allows for the interrogation of a relatively small number of genes. Because prostate cancer biopsies provide very limited tissue, there is interest in evaluating RNA expression platforms that could simultaneously integrate CCP genes and other less characterized targets that might be clinically useful. Here we evaluate the ability of microarrays to measure CCP gene expression. Methods: CCP scores for 1636 radical prostatectomy samples submitted for commercial testing were generated from the mean expression of 31 CCP genes and 15 housekeeping genes as determined by qRT-PCR. CCP scores were also generated from several publically available Affymetrix microarray expression data sets (Nakagawa et al. 2008, Karnes et al. 2013, Klein et al. 2014, Boormans et al. 2013, Taylor et al. 2013) by averaging the intensities (RMA processed, base 2 log scale) of the 31 CCP genes. Expression data were evaluated by comparing CCP score range and pairwise correlations between CCP genes. Results: The average pair-wise correlation in the commercial cohort using qRT-PCR was 0.67. The pair-wise correlations in the microarray studies were significantly lower, ranging from 0.17 (Klein) to 0.58 (Boormans). Importantly, the data in Boormans et al. was generated from frozen tissue. The CCP score in our commercial cohort ranged from -2 to 3 (base 2 log scale) with a standard deviation (SD) of 0.79. In contrast, the CCP score range in microarray studies was highly truncated with SDs ranging from 0.12 (Nakagawa) to 0.46 (Boormans). Conclusions: Expression of CCP genes as determined by microarrays correlates weakly with expression measured by qRT-PCR, with reduction in normally observed pairwise correlations among CCP genes and the range of CCP scores. This is especially true if the RNA is derived from fixed tissue. As a result, microarray generated CCP scores cannot be assumed to be a valid surrogate for qRT-PCR generated scores for prediction of patient outcome.
Integrated, structured reporting and diagnosis of localized prostate cancer.
Authors: Hofstraat Hans , Hoffmann Ralf , Janssen Marco , de Klerk Maud , Loos Marc , Jaederling Frederik , Akre Olof 
Published: September 2018

e16573 Background: To date 80-90% of men with primary prostate cancer are diagnosed with localized disease with a wide range of risks of future tumor progression. To optimize the balance between tumor removal and preserved continence and erectile function, it is essential to integrate all available information on tumor location, tumor characteristics, and baseline clinical data. Methods: We have developed a cloud-web-based technology allowing flexible access to the clinical data with close integration to the existing IT-environment like the hospital information management systems. The system allows the systematic and structured reporting of medical data generated by the involved disciplines of urology, laboratory, radiology, pathology, and (radiation) oncology, and patient reported health status and outcomes. Results: By use of the developed data integration platform we have collected diagnostic data of a prostate cancer case example scheduled for a multi-disciplinary primary treatment decision. The data comprises the patient health conditions, laboratory measures, multi-parametric MRI, localization information of MRI/US fusion guided biopsies, histo-pathology outcomes of prostate biopsy specimen, and patient reported outcomes on urinary and sexual function status. The collected data was presented in a visually integrated way and was used to discuss in a multi-disciplinary team, with the consistencies or discordances of findings across the various medical domains involved. Based on the discussion a primary treatment decision was concluded for this patient. Conclusions: The developed IT system to integrate heterogeneous medical data was successfully tested in a multi-disciplinary clinical setting. All required clinical variables to provide an informed primary treatment decision for a patient with primary localized prostate cancer was available in the system for discussion during the multi-disciplinary team (MDT) meeting and was presented in a clear visual way to support the interactive discussions between MDT members representing different clinical specialties.
Effects of exercise on dyspnea and cancer-related fatigue in patients with prostate cancer.
Authors: Cole Calvin , Peppone Luke Joseph , Kleckner Ian , Lin Po-Ju , Dunne Richard Francis , Fung Chunkit , Loh Kah Poh , Asare Matthew , Mustian Karen Michelle , Morrow Gary R. 
Published: September 2018

e16580 Background: Dyspnea and fatigue are two of the most common symptoms reported by patients with advanced cancer. Patients with dyspnea report an inability to complete activities of daily living (ADL) and impaired quality of life (QOL). Exercise has been shown to reduce cancer-related fatigue (CRF); however the relationships between dyspnea, CRF, ADL and QOL are unclear. The purpose of this study is to examine the effect of exercise on dyspnea, CRF, ADL and QOL. Methods: A secondary data analysis was performed on a two-arm randomized controlled trial investigating the influence of exercise on prostate cancer patients treated with hormone (androgen deprivation therapy) and/or radiation therapy. Exercise for Cancer Patients (EXCAP©) is a 6 week home-based program that includes progressive aerobic and resistance band training. Participants were randomly assigned to usual care with EXCAP© or usual care only (UC). Dyspnea, CRF, ADL and QOL were measured using the Multidimensional Fatigue Symptom Inventory (MFSI) and a Clinical Symptom Inventory (SI) at pre- and post-intervention. Results: Participants included 57 sedentary prostate cancer patients, average age 67 ± 8 years. Mean changes in dyspnea showed a positive, association with mean changes in CRF (SI r = .525; p < .01, MFSI r = .327; p = .08) in the EXCAP group but not in the UC group. Dyspnea changes were also positively associated with changes in exercise behavior (r = .590; p < .01), ADL (r = .684; p < .01), and QOL (r = .532; p < .01) in the EXCAP group, no association was found in the UC group. Furthermore, exercisers who reported the greatest improvements in dyspnea also reported greater improvements in CRF = 2.2 (p < .05), ADL = 1.8 (p < .01), and QOL = 2.4 (p = .01). Conclusions: Exercise-induced improvements in dyspnea are associated with improvements in CRF, ADL and QOL in prostate cancer patients. Additional research is needed to further understand these results. NCORP UG1 CA189961, R25 CA102618, DOD PC061518 Clinical trial information: NCT00815672.
Effect of PectaSol-C modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in patients (pts) with nonmetastatic, biochemically relapsed prostate cancer (BRPC): Results of the interim analysis of a prospective phase II study.
Authors: Keizman Daniel , Frenkel Moshe A. , Edwards Todd Michael , Rosenbaum Eli , Margel David , Sarid David , Neiman Victoria , Gottfried Maya , Maimon Natalie , Leibovitch Ilan , Dresler Hadas , Eliaz Isaac 
Published: September 2018

e16588 Background: 30% of pts with localized PC will have a biochemical relapse post local tx. The optimal tx of these pts remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long term benefit on survival remain undefined, and it is associated with significant cumulative toxicities.Thus evaluation of new non-toxic compounds in this pt population is warranted. P-MCP is a competitive inhibitor of galectin-3, a carbohydrate-binding protein, which is known to be involved in cancer pathogenesis. Preliminary pre-clinical and clinical data suggest that P-MCP is active in PC. We aimed to evaluate the safety and PSA dynamics of tx with P-MCP in pts with BRPC. Methods: Pts with non-castrate non metastatic BRPC were enrolled in a prospective phase 2 study of tx with oral P-MCP, at 4.8 grams X 3/day. Pts that did not progress clinically, biochemically (PSA), and radiologically, at 6 months (mos), were treated for subsequent 12 mos. Sample size provided 85% power to assess a decrease in PSA progression rate from 80% (natural history) to 40% (P-MCP tx) at 6 mos. We report here first results of a pre-planned interim analysis after ≤ 50% of planned enrolled pt completed 6 mos of tx. Results: The study was initiated in June 2013. We report here the 6 mos data of the first 35 pts enrolled. Median age was 74 years. Treatment of the primary tumor consisted of surgery in 11% (n = 4), radiation in 69% (n = 24), and both in 20% (n = 7). No pt had tx related grade 3/4 toxicity. One patient withdrew his consent after 1 mos. Of the 34 pts analysed, 18% (n = 6) had grade 1 toxicity. 62% (n = 21) had a stabilization/decrease of PSA, and negative scans, at 6 mo, and entered into the second 12 mos tx phase. A stabilization or improvement (increase) of PSA doubling time was noted in 79% (n = 27) of pts. Disease progression at 6 mos was noted in 38% (n = 13: PSA only 29%, n = 10; PSA and scans 9%, n = 3). A future final report will include full tx data (18 mos) and correlative analysis. Conclusions: The interim analysis of the present study suggests a potential benefit of P-MCP tx on progression of BRPC. P-MCP tx is safe. Final analysis is pending. Clinical trial information: NCT01681823.
Genetic diversity of HPV in tissues of tumors of the reproductive organs in women.
Authors: Nerodo Galina Andreevna , Kit Oleg Ivanovich , Zykova Tatiana , Ivanova Victoria A. , Nikitina Vera P. , Nerodo Ekaterina A. , Bogomolova Olga A. , Verenikina Ekaterina V. , Kravtsova Oksana E. 
Published: September 2018

e17001 Background: The purpose of the study was to determine the rate of various HPV genotypes detection in tissues of tumors of the female reproductive organs. Methods: FFPE and frozen tissue samples of cervical cancer (n=126), vulvar cancer (n=113) and uterine cancer (n=29) were studied. DNAs of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 were determined by the Real-Time PCR. Results: HPV DNAs were found in 94.4% of samples of cervical cancer tissue, 65.5% - uterine cancer tissue and 28.3% - vulvar cancer tissue. HPV 16 and 18 were the most frequent (78.8%). HPV 16 in cervical cancer was detected in 60.9%, vulvar cancer – 59.0% and uterine cancer – 54.5%. On the contrary, HPV 18 was more frequent in uterine cancer (40.9%) and less frequent in cervical cancer (18.4%) and vulvar cancer (2.7%). Besides HPV 16 and 18, genotypes 31, 33, 35, 39, 45, 51, 52, 56 and 59 were found in tumor tissues as well (21.2% in total). HPV 35, 52 and 56 were the most frequently detected. Cervical cancer tissues showed the greatest genetic diversity of HPV and uterine cancer tissues – the lesser one (HPV 35 only, besides HPV 16 and 18). Combination of several HPV types was also more frequent in cervical cancer (37.0% of positive samples); in vulvar cancer – 18.8% and in uterine cancer – 15.8%. Conclusions: The results confirm HPV significance in carcinogenesis of cervical cancer, vulvar cancer and probably uterine cancer and show genetic diversity of HPV in different localizations of tumors of the female reproductive system.
Dosimetric analysis of the effect of bladder volume on brachytherapy dose to organs at risk (OARs) in volume based intracavitary brachytherapy of carcinoma cervix: An institutional study.
Authors: Poddar Jyoti , Sharma Ashutosh Das , Suryanarayan K U , Shah Sonal Patel , Parikh Ankita 
Published: September 2018

e17006 Background: External beam radiotherapy combined with intracavitary brachytherapy is the standard of care in Carcinoma cervix. Due to its characteristics of rapid dose fall off, brachytherapy limits the toxicity to organs at risk while escalating radiation dose to target. Still, the organs near the radioactive source are at risk of considerable exposure, toxicity and post treatment morbidity. Alteration of bladder volume, alters the relative anatomy of uterus, rectum, sigmoid colon causing changes in the radiation dose to these organs. Methods: Aim:To correlate between the bladder volume and its effects on the dose received by bladder, rectum and sigmoid colon in volume based HDR brachytherapy in carcinoma cervix.30 patients (78 Intracavitary Brachytherapy applications) of Carcinoma Cervix (FIGO stage II-III) treated with EBRT followed by volume based HDR brachytherapy at our institute between July 2014 to Jan 2016 were studied. Bladder volume data was tabulated into five groups according to increasing volume of bladder. It was correlated with D2cc dose received by bladder, rectum and sigmoid colon. Results: Statistical Analysis Linear regression and correlation analysisof the HRCTV with dose to the bladder was 0.2 (.i.e HRCTV does not influence the bladder dose.) Pearson correlation of bladder volume and D2cc bladder and D2cc rectum was positive for all groups and for sigmoid D2cc was positive for group B and negative for all other groups. P value = 0.064 Conclusions: Keeping the bladder volume low (<130 cc) during brachytherapy would reduce the dose to bladder and rectum and the probability of late bladder and rectal toxicity reduces. [Table: see text]
Inhibition of EGFR nuclear translocation attenuate radioresistance through decreased p-DNA-PK expression in cervical cancer cells.
Authors: Qi Yunxiang , Lang Jinyi , Li Lu , Feng Mei , Huang Yecai 
Published: September 2018

e17011 Background: The commonly used treatment for cervical cancer is radiotherapy. However, the resistance to irradiation and metastasis at the advanced stage is a common reason for the poor prognosis and high mortality. This study was designed to elucidate the role of epidermal growth factor receptor (EGFR) nuclear translocation in radioresistance, and its correlation with DNA damage repair pathway in the cervical cancer cells. Methods: The dynamic expression of EGFR, DNA-dependent protein kinase (DNA-PK), PDK-1, PKN1 and their phosphorylation level in irradiated cervical cancer cell line CaSki at 0 10 20 40 minutes was determined by western blotting. Besides, nuclear localization signal (NLS) peptide inhibitor and control peptides was synthesized and treated cells before irradiation to elucidate the correlation between EGFR nuclear translocation and DNA damage repair after irradiation. Results: Expression of EGFR, protein kinase N1 (PKN1), and DNA-PK in nucleus was increased after irradiation in CaSki cells. Irradiation also enhanced the phosphorylation level of EGFR at Thr654, PKN1 at T774 and DNA-PK at T2609. Inhibition of EGFR nuclear translocation by NLS peptide decreased the expression level of EGFR and DNA-PK in the nucleus, and attenuated their phosphorylation process. Conclusions: EGFR nuclear translocation riggered by irradiation promoted DNA damage repair in irradiated cervical cancer cells. This work facilitated us to understand the possible molecular mechanism of the resistance to irradiation in the treatment of cervical cancer, providing a potentially potent clinical method to cancer therapy.
Therapeutic efficacy of epidermal growth factor receptor monoclonal antibody combined with concurrent chemoradiotherapy in treatment of locally advanced cervical cancer.
Authors: Chen Wenli , Li Tao , Zhang Wei , Yang Jialin , Wang Jian , Lang Jinyi 
Published: September 2018

e17012 Background: There are few studies about epidermal growth factor receptor monoclonal antibody nimotuzumab for the treatment of locally advanced cervical cancer. We aimed to assess the therapeutic efficacy and analyse prognostic factors of chemoradiotherapy combined with nimotuzumab in cervical cancer (stage IIB-IVA) . Methods: We retrospectively analyzed 23 patients with locally advanced cervical cancer(stage IIB-IVA) ,who received concurrent chemoradiotherapy combined with nimotuzumab from 2012 to 2014 (the study group) ,and 30 patients with the similar baseline characteristics who received concurrent chemoradiotherapy alone (the control group). The overall response rates, 5-year overall survival rates, progression-free survival and acute adverse events of the two groups were compared .Multivariate prognostic analysis was performed by a Cox proportional hazards model. Results: The median follow-up time were 46 months (IQR 16-60) in the study group and 42 months (2-60) in the control group.The overall response rates were 87% and 73.3% (P = 0.384) . The 5-year overall survival rates were 63.6% and 36.1% (hazard ratio 2.208,95% CI 0.878-5.557,P = 0.092) .The median progression-free survival in the study group was not achieved (95%CI 9-55) versus 27 months (1-60) in the control group (hazard ratio 2.635, 95% CI 1.030-6.737, P= 0.043).Multivariate prognostic analysis indicated that stage and whether to be combined with nimotuzumab were the influential factors for progression-free survival time.Adverse events were similar between groups.The most common grade 3 or 4 adverse events during treatment in the study group versus the control group were leucopenia(9 [39%] vs 11 [36%]),thrombocytopenia (3 [13%] vs 6 [20%]),anaemia (4 [17%] vs 4 [13%]). Conclusions: Concurrent chemoradiotherapy combined with nimotuzumab in the treatment can improve the progression-free survival time of advanced cervical cancer, while not increasing the incidence of adverse reactions.However, because of the small size of sample in this research, these findings suggest that it is necessary to perform a prospective study with expanded sample size.
Comparative effectiveness of laparoscopic radical hysterectomy for cervical cancer.
Authors: Lee Jung-Yun , Kim Jae-Weon , Kim Kidong , Lim Myong Cheol , Kim Jin Hee 
Published: September 2018

e17015 Background: Despite the benefits of minimally invasive surgery for cervical cancer, population-level data describing the surgery’s effectiveness in unselected patients are lacking. We compared morbidity, cost, and survival between abdominal radical hysterectomy and laparoscopic radical hysterectomy for cervical cancer. Methods: We used the Korean Health Insurance Review and Assessment Service database to identify women with cervical cancer who underwent radical hysterectomy from 2011 to 2014. Patient who underwent abdominal radical hysterectomy were compared with those who had minimally invasive hysterectomy. Perioperative morbidity, use of adjuvant therapy, and survival were evaluated. Results: We identified 6,335 patients including 3,235 who underwent abdominal radical hysterectomy and 3,100 who underwent laparoscopic radical hysterectomy. Uptake of laparoscopic radical hysterectomy increased from 46.1% in 2011 to 51.8% in 2014. Patients who were younger and treated at larger hospital were more likely to undergo laparoscopic procedure (P<0.001). Laparoscopic radical hysterectomy had lower rates of complication, less transfusion requirement, shorter hospital stays, and reduced total medical costs (P<0.001). There was no significant association between use of laparoscopic approach and recurrence-free survival (P=0.194). Conclusions: Laparoscopic radical hysterectomy was associated with lower risk of perioperative complication and have comparable outcomes with abdominal radical hysterectomy.