bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inherited germline mutations in men with prostate cancer.
Authors: Reid Robert , DiGiovanni Marcie , Bernhisel Ryan , Brown Krystal , Saam Jennifer , Lancaster Johnathan 
Published: September 2018

e16564 Background: Recent studies have demonstrated a high prevalence of pathogenic variants (PVs) in genes that confer hereditary cancer risk among men with metastatic prostate cancer (PC); however, PC does not currently receive attention as an indication for genetic testing. We assessed the clinical features of men with PC who received clinical testing as well as the distribution of PVs identified. Methods: A commercial laboratory database was queried to identify men with PC who underwent testing with a multi-gene hereditary cancer panel from September 2013–September 2016. Clinical information was obtained from provider-completed test request forms. Individuals with PC only were evaluated separately from those who had ≥1 additional malignancy. Personal/family history was evaluated relative to the 2013 NCCN guidelines for hereditary breast and ovarian cancer (HBOC) testing. Results: Overall, 700 men with a personal history of PC were identified: 384 (54.9%) with only PC and 316 (45.1%) with PC and ≥1 additional malignancy. The most common additional malignancies were colorectal (115) and breast cancer (105). The median age of diagnosis in men with only PC was 57.5, which is younger than tested men who had an additional malignancy (62) and the SEER data (2009-2013) for all men with PC (66). HBOC testing criteria were met by 75.9% of men, including 44 (6.3%) who met based only on a personal/family history of PC and 202 (28.9%) who met in part due to a personal/family history of PC. PVs were identified in 14.0% of all men: 11.5% of men with PC only and 17.1% of men with PC and a second malignancy (see Table). Conclusions: PC patients selected for genetic testing here were younger than men diagnosed with PC from the general population (SEER), and almost half had a diagnosis of an additional malignancy. They also have a high positive mutation rate across a broad spectrum of genes. [Table: see text]
Clinical variables associated with overall survival in metastatic castration resistant prostate cancer (mCRPC) patients treated with sipuleucel-T immunotherapy.
Authors: Wei Xiao , Perry Jaselle , Chang Emily , Zhang Li , Hiatt Robert A. , Fong Lawrence 
Published: September 2018

e16565 Background: Sipuleucel-T (Sip-T) is a cellular-based cancer immunotherapy for men with asymptomatic or minimally symptomatic mCRPC. Its approval was based on overall survival (OS) benefit in randomized placebo-controlled phase 3 trials. However, treatment was associated with PSA decline in only a small minority of pts. Understanding clinical factors predictive of OS may help to guide treatment decisions, including pt selection and timing of Sip-T relative to other therapies. Methods: This is a retrospective chart review of mCRPC pts treated with Sip-T at UCSF between April 2010 and April 2016. All pts completed 3 Sip-T infusions. Patients with localized prostate cancer treated with neoadjuvant Sip-T (NCT00715104) and pts with mCRPC treated with an ongoing phase 2 Sip-T/Ipilimumab trial (NCT01804465) were excluded. Kaplan-Meier method was used to estimate OS. The predictive value of candidate variables – including age, ECOG performance status (PS), Gleason score, metastatic volume, baseline PSA, baseline PSADT, prior abiraterone or enzalutamide, and prior chemotherapy – was assessed using univariate and multivariate Cox proportional hazard model. Results: Of 43 patients evaluated to date, 74.4% had ECOG PS 0, 88.4% had bone +/- nodal metastasis, 81.4% had low metastatic volume, 9.3% had prior abiraterone, 2.3% had prior enzalutamide, and 9.3% had prior chemotherapy. The median age was 69 years (range 53-85), median baseline PSA was 8.3 ng/mL (range 0.05-227.9) and median PSA doubling time (PSADT) was 3.9 mo (range 1.4-15.1). At a median follow-up of 21.4 mo, the median OS was 34.1 mo (95% CI 25.7-41.4). Univariate analysis showed that ECOG PS (HR 6.66, p < 0.001) and PSA (log-transformed) (HR 3.36, p = 0.002) were significantly associated with OS. There was a trend towards worse OS with faster baseline PSADT (log-transformed) (HR 0.16, p = 0.11) and prior chemotherapy (HR = 4.13, p = 0.11). By multivariate analysis, ECOG PS, baseline PSA and baseline PSADT were statistically significant (p < 0.05). Conclusions: In this ongoing retrospective cohort, ECOG PS, baseline PSA and baseline PSADT were associated with OS in mCRPC patients treated with Sip-T.
Retrospective correlational study between dyslipidemia and prostate cancer characteristics.
Authors: Sackey Korkor , Schwartzman Larisa , Shapero Stephen P. , Lewis Steven A. , Bruno Debora S. 
Published: September 2018

e16569 Background: Numerous studies have suggested metabolic syndrome’s association with advanced prostate cancer and patient outcomes but the data has not been conclusive. The goal of our research project was to analyze the relationship between lipid profiles and prostate cancer characteristics that predict outcomes in our patient population. Methods: A retrospective study was conducted on patients with a new diagnosis of prostate cancer seen at MetroHealth Medical Center (MHMC) between the years of 2009-2014. 427 electronic medical records of patients with stages I-III prostate cancer were reviewed. Dependent variables were pathological TNM stage, Gleason score (GS) and Prostate-Specific Antigen (PSA) level at time of diagnosis. Independent variables included components of the lipid profile (highest triglycerides, highest and lowest HDLs), body mass index, hypertension, diabetes and use of lipid lowering agents. Patients who did not have lipid panels available were excluded from final evaluation. Results: A total of 363 patients met inclusion criteria. The median age was 63, with African Americans accounting for 56% of all cases. The average BMI was 28.6 consistent with overweight and at time of prostate cancer diagnosis, 23% of patients had diabetes and 69% had hypertension. 68% of patients had stage I disease at time of diagnosis and no correlations were noted between TNM stage, GS or PSA at diagnosis with any of the components of the lipid profile, hypertension, hemoglobin A1c or use of lipid lowering medication. African Americans were noted to have higher PSA at diagnosis than other races (p < 0.0001). Conclusions: Of patients with stage I-III prostate cancer diagnosed between 2009-2014 at MHMC, 85% were screened for dyslipidemia. Preliminary analysis of our data did not establish a correlation between dyslipidemia and prostate cancer characteristics. However, by limiting our study to only patients with lipid profiles, a subset of patients and their characteristics were not analyzed. This could explain the results noted in our study. Further studies are needed in our population to investigate which factors affect prostate cancer characteristics so better screening and interventions can be developed.
The association of polymorphism in gonadotropin releasing hormone with serum testosterone level during androgen-deprivation therapy and prognosis in metastatic prostate cancer.
Authors: Shiota Masaki , Fujimoto Naohiro , Takeuchi Ario , Kashiwagi Eiji , Dejima Takashi , Inokuchi Junichi , Tatsugami Katsunori , Yokomizo Akira , Uchiumi Takeshi , Eto Masatoshi 
Published: September 2018

e16570 Background: Serum testosterone suppression during androgen-deprivation therapy (ADT) have been reported to affect ADT efficacy. However, the factor affecting hormonal variations during ADT was less explored. Therefore, in this study, we investigated the missense polymorphisms in gonadotropin releasing hormone (GNRH) and hormonal variations during ADT as well as the prognosis among men treated with primary ADT for metastatic prostate cancer. Methods: This study included 80 Japanese patients with metastatic prostate cancer, whose serum testosterone levels during ADT were available. The association of the GNRH1 gene polymorphism (rs6185, S20W) and the GNRH2 gene polymorphism (rs6051545, A16V) with clinicopathological parameters including serum testosterone levels during ADT as well as the prognosis including progression-free survival and overall survival was examined. Results: The CT allele and the CT/TT alleles in the GNRH2 gene (rs6051545) were associated with higher serum testosterone levels during ADT compared with the CC allele. Consequently, the CT alleles was associated with higher progression risk after adjustment with age and serum testosterone levels during ADT [hazard ratio (95% confidence interval), 1.73 (1.00-3.00), P = 0.049]. Conclusions: Taken together, these findings suggested that genetic variation in rs6051545 ( GNRH2) may result in the inadequate suppression of on serum testosterone during ADT, which may lead to detrimental effect of ADT on prognosis among men with metastatic prostate cancer.
Active surveillance and watchful waiting for localized prostate cancer in elderly patients >70 years in a community-based setting: Results from the HAROW study.
Authors: Herden Jan , Schnell Dietrich , Heidenreich Axel , Weissbach Lothar 
Published: September 2018

e16577 Background: Since more than half of patients with prostate cancer (PCa) are older than 70 years, this age group remains underrepresented in clinical trials. Possible non-invasive treatment options for these patients include Active Surveillance (AS) and Watchful Waiting (WW). In this prospective, non-interventional, health services research study, the use of different treatment options for localized PCa are observed under everyday conditions. The subgroups of patients ≥ 70 years, receiving AS- or WW are presented in terms of inclusion criteria, follow-up examinations and changes in treatment strategy. Methods: The study was conducted from July 2008 to July 2013 at 259 study centers in Germany, mainly office based urologists. The mean follow-up was 27.6 months. Clinical data (tumor category, digital rectal examination, PSA level, Gleason score, Charlson Comorbidity Index = CCI) and information about therapy and disease progression were collected at the time of study inclusion and subsequently at six-month intervals. According to the non-interventional study design, only recommendations were made for enrollment, course and discontinuation of AS and WW. The final therapeutic decision rested with treating physicians. Results: Overall, 2957 patients were enrolled, of whom 1165 were ≥ 70 years. 210 patients received AS and 87 patients received WW. AS patients were younger (73.9 vs. 76.8 years, p ≤ 0.001). The rate of low, intermediate and high risk tumors was 81.6%, 14.6% and 3.9% in the AS- and 39.1%, 43.5% and 17.4% in the WW-group (p ≤ 0.001). No differences were seen in the average number of PSA testing during the course of follow-up (AS = 3.97 vs WW = 3.79, p = 0.95). 37.6% of the AS patients and 12.4% of the WW patients received at least one follow-up biopsy. Conclusions: The results of HAROW indicate a clear distinction between AS and WW in terms of inclusion criteria. Interestingly, no clear distinction was seen in terms of follow-up examinations, since both groups were monitored frequently with PSA tests and even re-biopsies were performed in WW patients, neither of which is usually provided in WW programs.
Which is better? Carboplatin versus cisplatin for locally advanced cervical cancer: Peruvian experience.
Authors: Valdivieso Natalia , Paitan Amaro Victor , Rabanal Carretero Connie , Poma Nieto Nathaly , Flores Claudio J. , Vasquez Chavez Jule Franve , Alvarez Arredondo Manuel , Heredia Zelaya Adelaida , Mas Luis 
Published: September 2018

e17004 Background: Cervical cancer occurs mostly in developing countries, being locally advanced cancer the majority. The standard treatment is chemo-radiation with platinum salts. Carboplatin is commonly used because of its synergy with radiation reported in other malignancies and its safe toxicity profile, besides it is not clear use of it. We want to evaluate the equivalence of cisplatin versus carboplatin concurrent to radiotherapy in terms of response rates and toxicity profile. Methods: Retrospective observational analysis in women older than 18 years old, with diagnosis of locally advanced cervical cancer (stages Ib2 – IVA) at the “Instituto Nacional de Enfermedades Neoplasicas”, Lima – Peru, between 2014 and 2015. We determined two arms; cisplatin 40 mg/m2 per week for 5 weeks and Carboplatin 2AUC per week for 5 weeks. Both groups were given concurrent to radiotherapy. Results: 247 patients were evaluated, 119 received carboplatin and 128 cisplatin. Both groups have similar characteristics; median age was 50 years, the most frequent hystologic type was squamous cell carcinoma in 90.7%, and TNM stage IIB 59.5%, IIIB 27.5% and IV-A 2.8%. The complete response (CR) rate in cisplatin group was of 88.3% and carboplatin group 73.9% (p = 0.004). The toxicity profile was similar in both groups, except to renal toxicity (Cisplatin: 0% vs. Carboplatin: 5%, p = 0.010) and diarrhea (Cisplatin:26.6% vs. Carboplatin: 16.0%, p = 0.043). In patients with CR, the recurrence rate does not present a significant difference according to treatment schedule (Cisplatin: 15.9% vs. Carboplatin: 13.6%, p = 0.651). Overall survival (OS) and disease free survival (DFS) are on going. Conclusions: Our study found that cisplatin had better response rates than carboplatin with similar toxicity profile. This intervention to be remains to be clarified with following-up.
Changes in cervical cancer course under the influence of HPV/chlamydia trachomatis co-infection.
Authors: Guskova Nailya , Frantsiyants Elena Mikhaylovna , Bandovkina Valeria , Moiseenko Tatiana , Vovkochina Marina , Cheryarina Natalia D. , Pogorelova Yulia A. , Guskova Ekaterina , Vereskunova Marina I. , Avanesova Kristina , Tselishcheva Irina V. , Golomeeva Nadezhda , Abakumova Svetlana V. , Zakharchenko Viktoria , Belgova Svetlana V. , Nozdricheva Anastasia , Gornostaeva Ekaterina 
Published: September 2018

e17018 Background: The purpose of the study was to analyze the effect of HPV/Chlamydia trachomatis co-infection on the hormonal status of tumor and visually unchanged cervical tissues in cervical cancer patients. Methods: We studied levels of estrone (E1), estradiol (E2), free estriol (E3), free (fT) and total (T) testosterone, progesterone (P4) and prolactin (PRL) by the ELISA in tumors and visually unchanged cervical tissues of 49 patients with cervical cancer T1b-2aN0M0 with endophytic (25 patients) and exophytic (24 patients) patterns of tumor growth. 13 patients with endophytic tumors and 12 patients with exophytic ones were infected with HPV and Сhlamydia trachomatis (Ch.tr.). HPV infection was determined by Е7 protein expression, Ch.tr. – by IgG and IgА and antigen/DNA in ELISA and PCR. Intact cervical tissues obtained during hysterectomy from 22 non-infected women with endometrial cancer were used as the control. Results: Tumor tissues of the cervix without infection demonstrated increased levels of all sex steroids: estrogens by 3 times, androgens by 3.1 times and progestins by 1.8 times. Co-infected tissues were characterized by the sex-steroid imbalance. We observed reduced coefficients of estrogens to T and fT by 1.6 and 6 times, respectively, compared to intact tissues (most significant in a tumor with endophytic growth pattern) and an increase in the estrogens to P4 ratio by 1.5 times – only in endophytic growth pattern. Androgenic status in co-infected tumor tissues increased by 1.7 in endophytic and by 3.1 times in exophytic growth pattern. PRL level was increased only in co-infected tumors (by 2.5 times). Unchanged co-infected tissues, unlike non-infected samples, showed E2 increase by 2.6 times in exophytic and by 1.5 times in endophytic growth pattern, T increase by 1.6 times only in endophytic tumors and P4 decrease by 1.5 times and PRL increase by 1.8 times regardless the tumor growth pattern. Conclusions: Hormonal profile of both tumor and unchanged cervical tissues was dependent on HPV/Ch. tr. co-infection and tumor growth patterns. The changes could result from HPV and Ch. tr. interaction triggering malignant processes.
Investigation of the clinicopathological features of vulva cancer: A retrospective survey of the JGOG Net Work study.
Authors: Nishio Shin , Shibata Takeo , Yamaguchi Satoshi , Kanao Hiroyuki , Kojima Atsumi , Takekuma Munetaka , Tozawa Akiko , Tokunaga Hideki , Miyagi Etsuko , Kato Hisamori , Kurihara Kazuko , Yanase Toru , Mikami Mikio , Sugiyama Toru 
Published: September 2018

e17029 Background: Vulvar cancer is a rare malignancy in women. During the past 30 years, large surveys of vulva cancer have not been performed in Japan. We therefore conducted a multicenter study to clarify the clinicopathological features of vulva cancer in Japan. Methods: In this multicenter retrospective cohort study, the clinical data of patients with vulva cancer were surveyed. The medical records of patients with vulvar cancer patients treated between 2001 and 2010 were retrospectively reviewed after obtaining approval from the Institutional Review Board of each institution. Survival analysis was performed using Kaplan-Meier curves. The effects of the clinical factors on overall survival were investigated using a Cox regression model. Results: A total of 1082 patients treated in 108 centers were studied. The median age was 72 years (range, 20 to 96). The disease stage was stage I in 415 patients (38.3%), stage II in 249 (23%), stage III in 255 (23.6%), and stage IV in 163 (15.1%) (FIGO 2009). The diagnosis was squamous cell carcinoma in 779 patients (72%), Paget’s disease in 158 (14.6%), adenocarcinoma in 63 (5.8%), and others in 82 (7.6%). Positive lymph nodes were found in 237 patients (21.9%). The median tumor diameter was 35 mm (range, 1 to 180). The 5-year overall survival was 86% in stage I, 74.7% in stage II, 48.2% in stage III, and 39.3% in stage IV (P < 0.001), and that according to histology was 63.9% in squamous cell carcinoma, 57.1% in adenocarcinoma, 79.7% in Paget’s disease, and 85.4% in others. The hazard ratio was 0.51 in patients with a histology of Paget’s disease or others (vs. squamous cell carcinoma or adenocarcinoma; P = 0.001; 95% CI, 0.35-0.75), 2.14 in patients with a the number of positive lymph nodes 2 or more (vs. 0 or 1; P < 0.001; 95% CI, 1.50-3.05), 2.10 in patients with a tumor diameter of ≥35mm (vs. < 35mm; P = 0.001; 95% CI, 1.36-3.25). Conclusions: Treatment outcomes in Japanese patients with vulvar cancer were similar to those reported previously. However, squamous-cell carcinoma, adenocarcinoma, positive lymph nodes, and bulky tumors were associated with poor outcomes. Multidisciplinary treatment might be required in patients with these characteristics. Clinical trial information: UMIN000017080.
Interaction of α2-macroglobulin with kallikrein and plasmin in ascitic fluid in ovarian cancer.
Authors: Moiseenko Tatiana , Frantsiyants Elena Mikhaylovna , Kozlova Larisa , Tkalya Lyudmila Dmitriyevna , Adamyan Meri Viktorovich , Kravtsova Oksana E. , Chalabova Tatiyana Georgievna , Kit Oleg I. 
Published: September 2018

e17030 Background: The kallikrein (KLKs) family is considered to be a regulator of many systems of limited proteolysis but can also be involved into pathology. Plasmin (P) regulates functions and density of the extracellular matrix, angiogenesis, maturation of gametes, sanation of cavities, tissues and body fluids, development of inflammation and malignant tumors. α2-Macroglobulin (α2M) is a molecular component of the body's endogenous protection. Ascitic fluid (AF) in various diseases of the ovaries is the biological environment valuable for the study of the affected organism containing protein about 20-50 g/L. KLKs, their proenzymes (pro-KLKs), Р, plasminogen (PG) and α2М in AF are poorly studied. Our purpose was to analyze the proteinase-inhibitory balance in AF of patients with ovarian cystadenocarcinoma (CAC) and tuberculosis of the uterine appendages (TA) to reveal its role in the development of the diseases and targets for the therapy. Methods: KLKs, pro-KLKs, Р, PG and α2М in AF in CAC of one ovary (n=26, T3-4N0M0) were compared with the levels in AF of TA patients before treatment (n=11). All women were menopausal, aged 56.5±2.6 years. KLKs, pro-KLKs, Р, PG and α2М were determined before treatment using the U-2900 UV Solutions double-beam spectrophotometer (USA), the result was calculated per 1 mg of protein (by Lowry). The protein content in AF was comparable to the blood plasma one, so we took the values in the plasma of healthy donors as the norm (N). The data were processed using the Statistica 10 program. Results: The exudate is believed to occur mainly from inflammation-damaged vessels. High protein content in AF in CAC and TA allowed us to consider AF as the exudates. The pro-KLKs/KLKs ratio reflecting the rates of KLKs formation in AF was decreased in TA and CAC by 4.6 and 6.7 times compared to N. The РG/Р ratio in AF in CAC was decreased by 3.8 times; in TA it was similar to N with increased PG and P. The KLKs/α2М ratio in TA and CAC exceeded N by 4.6 and 2.7 times. The Р/α2М ratio in TA and CAC was 6.5 and 4.5 times higher than N. Conclusions: Activity of KLKs and P in AF in CAC and TA was higher than in the blood plasma of healthy donors. Activity of α2М in AF in CAC and TA was not sufficient to control KLKs and P.
Potential role of MAD1 1673G>A and ERCC1 8092C>A polymorphisms in the resistance to chemotherapy in advanced ovarian cancer: A pilot study.
Authors: Hernandez Cruz Irwin Alejandro , Prada Diddier , Díaz-Chávez José , Barquet-Munoz Salim , Cantu De Leon David Francisco , Herrera Luis Alonso 
Published: September 2018

e17045 Background: Ovarian cancer (OC) is the most lethal gynecological cancer and 70% of cases are in advanced stages at diagnosis. The standard treatment for those stages is optimal cytoreduction plus chemotherapy based on carboplatin-paclitaxel. Nevertheless, 60%-70% of patients will progress after diagnosis, becoming resistant in some point of the disease. There are no biomarkers to predict response to chemotherapy in OC. Some polymorphisms, including MAD1 1673G > A and ERCC1 8092C > A have shown potential to predict chemoresistance in other tumors. Thus, we explored the role of these polymorphisms in the resistance to chemotherapy in advanced OC. Methods: We genotypified 89 OC patients samples, and also determined the mRNA expression for both genes by RT-PCR. We compared distributions using chi-squared test and determined differences in overall survival and free-relapse survival using Kaplan-Meier curves and log-rank test. Results: Most of cases were IIIC stage (35.48%), papillary histological subtype (32.26%), highly differentiated (67.74%), and 35.48% tumors with recurrence. Distribution for MAD1 genotype was 35.48% for wild-type (WT), 32.26% for heterozygous (HT), and 32.26% for homozygous polymorphic condition (Poly). For ERCC1, we found a distribution of 25.81% for WT, 51.61% for HT, and 22.58% for Poly. When comparing distributions, we found statistically significant differences between sensitive vs. resistant tumors ( p= 0.02), with lack of the WT condition for ERCC1 in sensitive tumors. When analyzing haplotypes in regard to platinum-sensitivity, we also found statistical differences in the distribution of haplotypes ( p = 0.02). No association between genotypes and expression was observed. Remarkably, we found a lower free-relapse survival in the presence of at least one WT allele for the MAD1 polymorphism (p = 0.021, log-rank test). Conclusions: In this pilot study, we have found that ERCC1 8092C > A polymorphism, as well as haplotypes for these two genes, could be associated with chemoresistance. MAD1 1673G > A polymorphism could play also a role in recurrence in advanced OC.