bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal deletions, tumor phenotype, and prognosis in prostate cancer.
Authors: Minner S. , Krohn A. , Burkhardt L. , Tennstedt P. , Simon R. , Sirma H. , Huland H. , Sauter G. , Schlomm T. 
Published: February 2017

37 Background: Chromosomal deletions are frequent in prostate cancer (PCa) but target genes and potential clinical significance are often unknown. This project aimed at the identification of frequent and new deletions in PCa and to study their association with tumor phenotype and PSA recurrence. Methods: Array CGH was performed on 77 advanced PCa. Deletions of interest were subsequently analyzed on a tissue microarray containing more than 2000 PCa with clinical follow-up data using fluorescence in situ hybridization (FISH). The FISH probes used included a break-apart probe for TMPRSS2-ERG and dual-labeling probes for centromere 10/PTEN and centromere 3/3p14. Results: The most frequent circumscribed deletions found by array CGH were 3p14 (including FOXP1) in 18%, 5q31 in 16%, 5q21 in 14%, 6q13 in 21%, 6q21 in 19%, 6q26 in 14%, 8p11 in 17%, 10q23 (including PTEN) in 18%, 12p13 in 14%, 13q14 in 14%, 16q24 in 22% and 21q (representing TMPRSS2-ERG fusion) in 18%. TMPRSS2-ERG fusions, PTEN and FOXP1 deletions were selected for FISH analysis. A TMPRSS2-ERG fusion was observed in 394 of 947 interpretable cases (41.6%). TMPRSS2-ERG fusion was unrelated to tumor stage, Gleason grade, and PSA recurrence. PTEN deletions were observed in 8.9% of 1844 interpretable cases and were associated with advanced tumor stage (p<0.0001), high Gleason grade (p<0.0001), and early biochemical recurrence (p<0.0001). FOXP1 deletions were seen in 5.0% of 619 cases. FOXP1 deletions were not significantly linked to tumor phenotype and outcome. Both PTEN and FOXP1 deletions were strongly linked to TMPRSS2-ERG fusions. TMPRSS2-ERG fusion positive tumors had PTEN deletions in 15.4% and FOXP1 deletions in 10.7%, while TMPRSS2-ERG fusion negative cancers had PTEN deletions in only 5.8% and FOXP1 deletions in only 2.0% of cases (p<0.0001 each). Conclusions: The TMPRSS2-ERG fusion determines a genetically distinct subgroup of prostate cancers. Our data provide no evidence for a particular clinical behaviour of TMPRSS2-ERG fusion positive cancers in radically operated patients. PTEN and FOXP1 alterations are preferentially found in TMPRSS2-ERG fusion positive cancers. Both genes may potentially be involved in pathway dysregulation in these cancers. No significant financial relationships to disclose.
An underinvestigated toxicity of sunitinib: Red cell macrocytosis.
Authors: Hands D. J. , Eccles B. , Geldart T. R. 
Published: February 2017

371 Background: Sunitinib, a multitargeted receptor tyrosine kinase inhibitor represents a standard firstline therapy for advanced renal cell carcinoma. Red blood cell (RBC) macrocytosis (with or without anaemia) is a recognized haematological toxicity but its aetiology remains uncertain. Methods: The medical records of 73 patients (55 male, 18 female) patients treated with sunitinib between 2007 and 2010 at Poole and Bournemouth NHS Trusts, UK were reviewed. Patient demographics, length of treatment, response, RBC mean cell volume (MCV) indices, and known causes of macrocytosis including B12 and folate deficiency and hypothyroidism were examined. Results: Median duration of treatment was 6 months (range 0-30). 38 (51%) have died. 24 (32%) received 2 or less cycles of treatment with the majority stopping due to early progression or death. 30 patients (41%) developed macrocytosis on treatment, but a trend to macrocytosis was identified in most patients positively correlating to time on treatment. 26 (87%) had a macrocytic anaemia. Median time to onset of macrocytosis was 4 months (range 1-11 months). Of the 30 macrocytic patients; 5 were hypothyroid, 7 had untreated borderline hypothyroidism and 13 were euthryoid throughout. Of patients tested to date 1 patient was found to be serum folate deficient at 2.5 ug/L (3-17). Supplementation corrected the macrocytosis. 1 patient was found to be serum B12 deficient; 53 ng/L (180-900) without any obvious comorbid cause. Further retrospective evaluation of other parameters such as red cell folate and reticulocyte count are currently being carried out. Conclusions: A significant proportion of patients on sunitinib (41%) develop macrocytosis. On the basis of this case series, the largest to date, underlying causes of macrocytosis (with or without anaemia) appear multifactorial. Biochemical hypothyrodism is common following sunitinib treatment and is likely to represent one of several possible contributing factors. B12 and folate deficiency should not be forgotten as a potentially reversible cause of macrocytosis secondary to sunitinib. C-kit inhibition by sunitinib is a potential mechanism, paralleling the potential C-kit mediated macrocytosis commonly recognised in imatinib therapy. No significant financial relationships to disclose.
Survival outcomes in metastatic renal carcinoma based on histological subtypes: SEER database analysis.
Authors: Didwaniya N. , Edmonds R. J. , Fang X. , Silberstein P. T. , Subbiah S. 
Published: February 2017

381 Background: Renal cell cancer (RCC) represents a heterogeneous group of tumors with distinct histopathologic, genetic, and clinical features. This study was conducted to evaluate the prognostic value of histology in RCCs. Methods: 3,062 patients with metastatic RCC from year 1998-2007 were identified from Surveillance Epidemiology and End Results (SEER) database. Data regarding their age, sex, race, treatment modality utilized and cancer specific survival was extracted and analyzed. Results: Clear cell, sarcomatoid, adenocarcinoma NOS, papillary, collecting duct, chromophobe and cyst associated renal carcinoma accounted for 2,166 (70%), 433 (14%), 216 (7%), 160 (52%), 47 (1.5%), 35 (1.14%), and 5 (0.01%) respectively. The mean age of presentation was 63.5 in clear cell RCC and 62.7 years in non-clear cell RCC. Surgery was performed in 57.23% of all clear cell cancers and 50.84% in non-clear cell-RCC group. 27.34% of all clear cell cancer patients received radiation in contrast to 34.53% in the other group. Both clear cell RCC (64.54%) and non-clear cell RCC (69.52%) occurred commonly in males. Incidence of clear cell RCC was 4.67% in Asians, 7.01% in Blacks, 88.32% in Whites. The incidence of non-clear cell RCC was 3.81% in Asians, 14.78% in Blacks, and 81.41% in Whites. Cancer-specific survival was calculated in all histologic subtypes. Median survival for clear cell RCC was 8 months, 3 months for adenocarcinoma NOS, 7 months for cyst associated renal carcinoma, 8 months for papillary carcinoma, 7 months for chromophobe type, 4 months for sarcomatoid and 4 months for collecting duct RCC. Median overall survival was significantly better for clear cell cancer as compared to non-clear cell RCCs (8 months vs. 4 months; p< 0.0001). Conclusions: Non-clear histology RCCs represent 30% of metastatic RCC and are associated with poor prognosis when compared to clear cell RCC.While development of novel targeted therapies has improved survival in clear cell RCC, it has not made a impact in survival of non-clear RCCs. An indepth understanding of the genetic and molecular changes associated with non-clear cell RCCs is important to improve their prognosis. No significant financial relationships to disclose.
Pheochromocytoma (PC)/paraganglioma (PG) and sunitinib: Review of reported cases and literature and case report contribution.
Authors: Dettino A. A. , Guimaraes G. C. , Formiga M. , Rinck J. , Ribeiro A. G. , Alves M. S. , Rameri C. , Serrano S. C. , Pagano T. , Fanelli M. F. 
Published: February 2017

406 Background: Pheochromocytomas/paragangliomas (PC/PG) are rare diseases, but may be responsible for lower quality of life to patients,if progressive or metastatic when malignant. Recently, some benefit has been reported with the use of palliative tyrosine-kinase inhibitors (TKI),such as sunitinib, already approved for kidney cancer. Methods: Review of litearure with a Medline search for PC/PG and suninitib, due to the need to treat a patient with progressive advanced malignant PC, refractory to chemotherapy (CT). Our plan is to contribute reporting safety and efficacy in an additional PC patient. Results: We expose the data found in a table below,with most relevant features related to PC/PG treatments and TKI. Conclusions: Sunitinib as a treatment option to refractory PC/PG may be active and should be further evaluated in this context. A phase II trial is under way (SNIPP; NTC00843037). Other therapies may be evaluated, such as sorafenib, bevacizumab, temozolomide, temsirolimus, thalidomide, and other potential molecular strategies, also with other small molecules, target therapies, and antiangiogenic factors. We plan to follow the reported PC patient and show additional data in the near future. [Table: see text] No significant financial relationships to disclose.
Parafibromin as a new immunohistochemistry staining to improve pathologic diagnosis of renal oncocytoma: Analysis of 225 renal tumors.
Authors: Albiges L. , Couturier J. , Allory Y. , Camparo P. , Sibony M. , Vieillefond A. , Teh B. T. , Escudier B. J. , Molinie V. ,   GELU
Published: February 2017

408 Background: Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma (Onc) are two distinct but closely related entities with strong morphologic and genetic similarities. While chRCC is a malignant tumor, Onc is usually considered as a benign entity. Recently, gene expression profiling applied on chRCC and Onc identified new potential markers that may effectively discriminate the 2 pathologic entities, including parafibromin. This work aims at evaluating the diagnostic value of Parafibromin (Pf) immuno staining on a large number of renal tumor samples. Methods: Sixty-three renal clear cell carcinoma (ccRCC), 47 papillary (Pap), 40 chRCC, and 75 Onc were immunostained for parafibromin antibody (1/200; Santacruz Biotechnology), on a tissue micro array. Results: Parafibromin was positive in 38.6% of Onc, vs 5% of chRCC (p < 0.001), with a 95% specificity, and the positive predictive value observed for parafibromin was 94%. For other tumor types, a positive staining for parafibromin was observed in 7.9% and 8.5% in ccRCC and Pap respectively. Conclusions: Parafibromin is a recently identified protein which seems to be specific for oncocytoma, and highly discriminant for other histologic renal cell tumor subtypes, especially for chromophobe. IHC may help to optimize therapeutics strategy for small renal mass and avoid surgical resection of benign lesions in some patients.Validation of this staining on renal tumor biopsies is on going.The value of the combination of this new immunostaining associated with the three standard IHC staining (CK7, CD117, E Cad) will be provided at the meeting. [Table: see text] No significant financial relationships to disclose.
Do urologists and radiation oncologists agree on adjuvant radiation therapy for prostate cancer? A web-based patterns-of-care survey.
Authors: Showalter T. N. , Teti K. A. , Foley K. A. , Keith S. W. , Trabulsi E. J. , Dicker A. , Lallas C. D. , Pizzi L. , Gomella L. G. 
Published: February 2017

76 Background: Three randomized trials support adjuvant radiation therapy (ART) over observation after radical prostatectomy (RP) for prostate cancer (PC) patients with adverse pathologic features (APFs), but many clinicians instead favor early salvage RT (SRT) for a rising PSA. We conducted a web-based survey of U.S. radiation oncologists (RO) and urologists (U) regarding ART and SRT. Methods: We designed a web-based survey to evaluate beliefs about post-RP RT and treatment policies. Survey invitations were e-mailed to SUO members and a list of 926 RO ASTRO members with an interest in PC. One email was sent to limit message burden. Only those responses at least 50% complete were included in the analysis. Differences in ART recommendation rates were evaluated by chi square test. Results: Responses were received from 231 RO and 101 U, resulting in 302 analyzable responses (88 U, 214 RO). 79% of U and 32% of RO respondents were academic physicians. ART was recommended based on APF alone (78% RO, 44% U), based on APF plus Gleason score or PSA (14% RO, 35% U), only for detectable PSA (7% RO, 14% U), or never (2% RO, 7% U). When asked the effect of ART on outcomes, most respondents replied “improves survival” (71% RO, 63% U) or “improves biochemical control but not survival” (29% RO, 30% U), but 9% of U replied “delays PSA recurrence, but no durable benefit” or “no improvement in any outcomes” (versus 0% RO). A recommendation for ART based on APFs alone was made for: seminal vesicle invasion (SVI) (76% RO, 59% U; p=0.003), extracapsular extension (ECE) (70% RO, 32% U; p<0.001), positive surgical margin (PSM) (91% RO, 48% U; p<0.002). For patients with Gleason score 8-10 PC, ART was recommended for: SVI (75% RO, 56% U; p=0.001), ECE (73% RO, 45% U; p<0.001), PSM (93% RO, 74% U; p<0.001). Reported PSA threshold for SRT was: any detectable (36% RO, 23% U), 0.2-0.3 (50% RO, 36% U), 0.4-0.5 (9% RO, 30% U), 0.6-0.8 (3% RO, 10% U) ng/mL, or higher (1% RO, 1% U). Conclusions: Despite similar rates of belief that ART improves survival or biochemical control, U were less likely than RO to recommend ART based solely on APFs after RP. Upcoming results of clinical trials of ART versus SRT may provide consensus for decisions in this setting. No significant financial relationships to disclose.
Correlation of radiotherapy with cause-specific and overall survival in clinically node-positive prostate cancer.
Authors: Tward J. D. , Shrieve D. C. 
Published: February 2017

9 Background: Clinically staged node-positive prostate adenocarcinoma is a rare entity. We evaluated the role of definitive radiotherapy (RT) in clinical N1 prostate cancer patients who did not undergo prostatectomy and compared their cause-specific (CSS) and overall (OS) survival to men who did not undergo any definitive therapy. Methods: Subjects were identified using the NCI's Surveillance, Epidemiology and End Results (SEER) Program diagnosed between the years 1988 and 2006 with adenocarcinoma of the prostate. Subjects included in the analysis were men with clinically staged node-positive disease, who were otherwise non-metastatic. Descriptive statistics were performed, and CSS and OS was estimated using the methods of Kaplan and Meier. Statistical comparisons of treatment modalities were analyzed using univariate and multivariate Cox regression. Results: A total of 1,100 subjects were identified. The median age was 69 yrs (range 41-95) and median f/u time was 90 months (range 1-255 months). The 5, 10 and 15 yr CSS for men who had no definitive therapy was 71.1%, 50.3% and 35.1% respectively. The 5, 10 and 15 yr CSS for men who had external beam RT was 78.1%, 62.9% and 51.4% respectively. This was significantly different favoring RT on univariate cox regression (Hazard Ratio (HR) =0.66, 95% CI=0.54 to 0.82, P = 0.0002). The 5, 10 and 15 yr OS for men who had no definitive therapy was 56.2%, 29.1% and 14.86% respectively. The 5, 10 and 15 yr OS for men who had external beam RT was 67.8%, 44.2% and 20.4% respectively. This difference was also significant favoring RT on univariate cox regression (HR =0.70, 95% CI 0.59 to 0.81, P < 0.0001). On multivariate Cox regression analysis taking into account age at diagnosis, Gleason sum 2-4, 5-7, and 8-10, year of diagnosis, and presence or absence of definitive RT, RT (HR=0.69, 95% CI=0.56 to 0.86, P = 0.0008), earlier year of diagnosis (HR=0.94, 95% CI=0.92 to 0.97, P < 0.0001), and GS 7 or less was correlated with improved CSS. Conclusions: RT for node-positive subjects is correlated with both clinically and statistically improved cause-specific and overall survival. Patients with clinical N1 prostate adenocarcinoma should be strongly considered for RT. No significant financial relationships to disclose.
Dose to regions within the prostate during the learning curve phase in low dose rate (LDR) brachytherapy: Sector analysis of 71 consecutive patients at Princess Margaret Hospital.
Authors: Saibishkumar E. P. , Iupati D. , Borg J. , Fernandes K. 
Published: February 2017

91 Background: It is important to evaluate the dose distribution within the prostate in highly conformal and operator dependent treatment like brachytherapy, especially in the learning curve phase when technical skill is evolving. We report detailed dosimetric analysis of prostate sectors in the initial 71 consecutive implants performed by a physician in the first year of practice. Methods: Implants were done based on a pre plan but intra-operative adjustments were made to account for actual seed positions and addition of seeds and the final dose distribution to the prostate was documented as Intra-operative (IO) plan. Post-implant assessment was at 1 month using fused MRI/CT scans. Twelve prostate sectors were generated by division into 4 quadrants (anterior, posterior, laterals) and 3 segments (base, middle and apex). IO and post-implant (PI) V100 and D90 for sectors and whole prostate were recorded. Comparative (Wilcoxon Rank Sum) and association (Spearman's rank correlation) testing was performed for univariate analysis. Optimal dosimetry values for the entire prostate and sectors were defined as D90 >90% and V100 >85%. Results: Seventy implants were optimal (out of 71) with mean prostate PI V100 and D90 of 95.5% and 117.1%. Only 1 sector had suboptimal mean PI V100 and D90 (70.3% and 85.9%), significantly lower than IO (p<0.001), contributing to lower PI V100 for the base (88%) and anterior sectors (86.9%). The mean IO D90 of apical sectors (126%) was lower than base and mid gland (131% and 132% respectively) and lateral sectors was (134%) higher than anterior and posterior sectors (123% and 126%) consistent with a modified peripheral loading approach. D90 decreased from IO to PI plan in anterior (123% vs 106%, p<0.001) and base sectors (132% vs 108%, p<0.001) while increase was noted in apical (126% vs 133%, p<0.001) and posterior sectors (126% vs 131%, p=0.006). Conclusions: Results are encouraging with optimal dosimetry in 11/12 sectors in most patients, and sector analysis provided insight into planning factors and provided useful data for refinement in practice. Further study correlating sector analysis with clinical outcomes is required. No significant financial relationships to disclose.
Optimized response prediction in esophagogastric junction adenocarcinomas (EGJAc) with combination of molecular biomarkers and FDG-PET.
Authors: Petty Russell David , Bain Gillian H , Murray Graeme I , Gilbert Fiona Jane , Denison Alan , Mckiddie Fergus , Ahearns Trevor , Leeds John , Phull Perminder , Park Ken , Nanthakumaran Shayanthan , Welch Andy , Schweiger Lutz , Collie-Duguid Eliana 
Published: February 2017

1 Background: Predictive biomarkers (BMs) for EGJAc would optimise treatment selection and avoid ineffective therapy. Metabolic response (MR) defined as >35% decrease in tumour FDG Standardized Uptake Value (SUV) between day 0 & 14 after starting chemotherapy has a high negative predictive value (95%) for response, but limited positive predictive value (50%). Combining molecular BMs with FDG-PET may optimise response prediction. We used global gene expression profiling (GEP) to identify molecular BMs that when combined with FDG-PET would improve predictive accuracy. Methods: 28 patients with locally advanced or metastatic EGJAc received platinum based chemotherapy (PBC). FDG PET CT scans were at day 0 and day 14 and GEP (Affymetrix ST1.0 Exon Genechips) on day 0 tumour biopsies. A tissue microarray comprising an independent set of 154 OGJAc who underwent surgery +/− neoadjuvant PBC was used with immunohistochemistry (IHC) for qualification of GEP results. Radiological response was assessed after 3/ 4 cycles of PBC by RECISTv1.1. Results: We identified a gene expression signature (86 genes) that separated FDG PET MR patients(>35% fall SUV day 0 to14) into those that do and do not go on to have a RECIST response. In cross validation, this signature correctly predicted response in 28/28. Pathway analysis on GEP data identified potential novel mechanisms of response, including the Leptin pathway. Leptin mRNA was higher in FDG metabolic responders who did not have a RECIST response compared to those that did. In the independent set, high Leptin protein by IHC was strongly associated with lack of histopathologic response to neoadjuvant PBC (n=64, p=0.002). High Leptin expression also had a therapy independent prognostic effect with longer survival in the absence of histopathologic response or with no neoadjuvant PBC and in low Leptin patients poor survival was mitigated to a certain extent by neoadjuvant PBC (n=154, Kaplan-Mieier, log rank p=0.041 & Cox MVA p=0.040). Conclusions: Molecular biomarkers (Leptin in particular) combine with FDG PET to optimise response prediction in EGJAc. Further investigation of this combined molecular and imaging approach is warranted.
Regional differences in patient (pt) characteristics of AVAGAST: An exploratory comparison in chemotherapy plus placebo (PL) arm between Japanese (JPN) and the rest of the world (ROW) pts.
Authors: Nishina Tomohira , Sawaki Akira , Yamaguchi Kensei , Doi Toshihiko , Yamada Yasuhide , Chin Keisho , Satoh Taroh , Boku Narikazu , Omuro Yasushi , Komatsu Yoshito , Takiuchi Hiroya , Hamamoto Yasuo , Koizumi Wasaburo , Saji Shigehira , Shah Manish A. , Van Cutsem Eric , Kang Yoon-Koo , Ohtsu Atsushi 
Published: February 2017

100 Background: AVAGAST study showed regional differences in efficacy, including notable differences in progression free survival (PFS) and overall survival in the PL arm. In Japan, there is a certain number of pts with minimal peritoneal metastasis (PM) diagnosed only by laparoscopy or open surgery, which seems unusual in Western as well as in other Asian countries, and it might have led the differences. Therefore, an exploratory analysis was conducted among the PL arm to examine pt characteristics including PM associated with differences in outcome between JPN and ROW. Methods: We compared PFS of PL arm between pts enrolled from JPN and those from ROW. Hazard ratio (HR) and its 95% confidence interval (95%CI) between JPN and ROW were calculated using Cox’s proportional hazard model for each major covariates (disease status, performance status, prior gastrectomy, prior (neo)adjuvant chemotherapy, age, sex, primary site, liver metastasis (mets), number of metastatic sites, disease measurability, histologic type, maximum of tumor size, sum of tumor size, bone mets, PM and only PM) Results: 188 pts from 14 sites were enrolled from JPN, of which 94 pts were randomized to PL arm. Compared with 293 pts from ROW in PL arm, PFS tend to be favorable in JPN. Subgroups of JPN without liver mets, with diffuse or mixed type gastric cancer (GC), with PM and with only PM were clearly favorable than that of ROW. The difference in subgroup with PM was especially large with lower confidence limit of 1.21. When the pts with only PM were excluded, the difference of PFS in PL arm between JPN and ROW became smaller ( Table ). Conclusions: In this exploratory analysis, pts with PM in JPN had a better prognosis than ROW pts. Understanding this unique pt population may provide insight to the regional differences in outcome noted on this study. [Table: see text]