bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overall survival of men with metastatic castration-resistant prostate cancer (mCRPC) receiving first-line docetaxel-containing chemotherapy according to their participation (or not) in clinical trials.
Authors: Goyal Jatinder , Huang Peng , Tyagi Prachi , Oh Daniel , Carducci Michael Anthony , Eisenberger Mario A. , Antonarakis Emmanuel S. 
Published: February 2017

148 Background: There is insufficient evidence to determine whether clinical trial participation can itself lead to improved clinical outcomes in patients with mCRPC treated with docetaxel chemotherapy. We compared clinical characteristics and survival outcomes of patients with mCRPC receiving first-line docetaxel-containing therapy on a clinical study (trial participants) or outside of a clinical trial (non-participants). Methods: We retrospectively reviewed the records of 245 consecutive chemotherapy-naïve patients with mCRPC who received docetaxel-containing therapy between 1/1/1998 and 1/1/2010, either as trial participants (n=142; 11 separate studies) or as non-participants (n=103). Patient demographics, baseline clinical characteristics, treatment details and follow-up data were recorded. Results: In unadjusted analysis, trial participants were more likely to be white (83 vs 70%, p=0.005), to have better ECOG performance status (p=0.01), higher baseline hemoglobin (12.4 vs 11.6 g/dL, p=0.0003), higher albumin (4.3 vs 4.0 g/dL, p=0.009), lower creatinine (0.90 vs 1.04 mg/dL, p=0.01), and to have received a higher number of chemotherapy cycles (6.6 vs 5.1, p=0.001) than non-participants. In Kaplan-Meier analysis, median overall survival was significantly longer among trial participants vs non-participants (21.3 vs 17.1 months, p=0.024). In multivariable analysis, trial participation (HR 0.53, p=0.013), more chemotherapy cycles (HR 0.87; p=0.0002), baseline hemoglobin >12 g/dL (HR 0.67, p=0.016), lower ECOG score (HR 0.57, p=0.026) and lower baseline (log) PSA (HR 0.85, p=0.012) were all found to be independent predictors of survival. Conclusions: Clinical trial participation is an independent positive predictor of overall survival in men undergoing first-line docetaxel-containing chemotherapy for mCRPC. Improved survival in trial participants may reflect better medical oversight typically seen in patients enrolled in clinical trials, more regimented follow-up schedules, or a positive effect on caregivers’ attitudes due to greater contact with medical services.
Promoting consultation recording practice in oncology: Identification of critical implementation factors and determination of patient benefit.
Authors: Hack Thomas F , Ruether Joseph D. , Weir Lorna , Grenier Debjani , Degner Lesley F 
Published: February 2017

155 Background: The objectives of this implementation study were to 1) identify and address the evidentiary, contextual, and facilitative mechanisms that serve to retard or promote the transfer and uptake of consultation recording use in oncology practice, and 2) follow patients during the first few days following receipt of the consultation recording to document, from the patient’s perspective, the benefits realized from listening to the recording. Methods: Nine medical and 9 radiation oncologists from cancer centers in three Canadian cities (Calgary, Vancouver, Winnipeg) recorded their primary treatment consultations for 228 patients newly diagnosed with prostate or breast cancer. The Digital Recording Use Semi-Structured Interview (DRUSSI) was conducted at two days post-consultation and at 1-week post-consultation. Each oncologist was given a feedback letter summarizing the consultation recording benefits reported by their patients. Results: Sixty-nine percent of patients listened to at least a portion of the recording within the first week following the consultation. Consultation recording favourableness ratings were high: 93.6% rated the intervention between 75–100 on a 100-point scale. Four main areas of benefit were reported: 1) Anxiety reduction; 2) Enhanced retention of information; 3) Better informed decision making; and 4) Improved communication with family members. Eight fundamental components of successful transfer and uptake of consultation recording practice were identified. Conclusions: Implementation research and additional randomized trials are needed to facilitate the transfer and uptake of consultation recording use so that far more patients and significant others may realize the associated benefits.
Active surveillance for prostate cancer: Scottish experience.
Authors: Ansari Jawaher , White Lillian , Glen Hilary , McGlynn Brian , Nairn Robert , Balsitis Margaret , Hollins Graham , Smith Kathleen , Nair Biju , Gurun Murat , Little Brian , Meddings Robert , Al-Saffar Neil , Hussain Syed A. , Glaholm John , Mahmood Rana I. 
Published: February 2017

167 Background: Prostate cancer is the second most common malignancy in men worldwide with 910,000 cases registered in 2008. The prognosis for low-risk prostate cancer patients remains excellent and arguably the majority may either not require radical treatment or may benefit from deferred radical treatment. Active surveillance involves serial prostate-specific antigen (PSA) monitoring, digital rectal examinations, and periodic trans-rectal ultrasound guided prostate biopsies. Patients for active surveillance are carefully selected, counselled and actively followed-up. Radical treatment is deferred until there is evidence of biochemical, pathological or clinical disease progression. Methods: Retrospective review of prostate cancer patients enrolled on to the active surveillance program within NHS Ayrshire and Arran Hospitals. Clinical examination and PSA monitoring was undertaken 3-monthly in year 1, 4-monthly in year 2 and 6-monthly thereafter. The protocol stipulates repeat TRUS biopsies at years 1, 4, 7 and every 3 years thereafter. Results: 105 patients with low-intermediate risk prostate cancer with a median age of 68yrs (48–78yrs) were followed for a median duration of 30 months (4–152 months). The median PSA at presentation was 7ng/ml (0.5-31). Repeat biopsies were performed in 82 patients and 37% had no histological evidence of cancer. The median time to re-biopsy was 16 months (10–85 months). Of the patients who received radical treatment; 3 underwent radical prostatectomy and 23 received radical radiotherapy. The indications for radical treatment were pathological progression in 73%, PSA progression in 23% and co-existing bladder cancer in 4%. One patient died due to unrelated medical problems and one patient developed metastatic disease. Conclusions: With appropriate counselling, a significant percentage of men with low-moderate risk prostate cancer choose active surveillance. In this study, active surveillance does not appear to compromise outcomes for patients with low-intermediate risk prostate cancer. Less then 25% of patients needed radical treatment and therefore this approach appears cost-effective and avoids treatment-related morbidity.
Response to abiraterone acetate in the postchemotherapy setting in patients with castration-resistant prostate cancer whose disease progresses early on docetaxel.
Authors: Mukherji Deborah , Pezaro Carmel Jo , Bianchini Diletta , Zivi Andrea , De Bono Johann Sebastian 
Published: February 2017

17 Background: Abiraterone acetate (AA) has recently been approved for men with metastatic castration-resistant prostate cancer (CRPC) following docetaxel chemotherapy. AA inhibits CYP17, reducing androgen production and thereby impacting androgen receptor (AR) signalling. Recent evidence suggests taxanes also impact AR signalling, raising concerns about potential cross-resistance. We have previously shown that docetaxel has no antitumor activity in AA refractory patients. We have now evaluated the antitumor activity of AA post-docetaxel to determine the activity of AA in docetaxel refractory patients. Methods: Forty four men with CRPC treated with docetaxel (75 mg/m2 every 21 days) followed by post-chemotherapy AA at the Royal Marsden Hospital were identified. Radiological response by RECIST, PSA response by PSAWG2 criteria and symptomatic benefit were evaluated. Results: An average of 9 cycles of docetaxel were given (range 3-17); 7 patients discontinued chemotherapy due to progression of disease and 10 for toxicity. Of 40 patients with PSA data available, 26 (65%) had a PSA decline of at least 50%. At commencement of AA, median age was 68 years. Bone, nodal and visceral metastases were present in 38 (86%), 23 (52%) and 6 (14%) of the cohort respectively. An average of 5 months of treatment were delivered and 23 patients continue on AA. Of the 44, 7 (16%) patients had a 50% or greater PSA decline on AA. None of the 7 patients who were docetaxel refractory had a subsequent PSA, radiological or clinical response to AA. Of the 6 patients who received less than 5 cycles of docetaxel due to toxicity, 2 had subsequent PSA response on AA. There was no relationship between length of time on LHRH agonist and PSA response to AA. Conclusions: Our data suggest that patients who are refractory to docetaxel do not respond to AA. Overall, in conjunction with our other evidence that in AA-refractory patients docetaxel has no antitumor activity, these data provide further evidence for cross-resistance between these two agents.
Volumetric modulated arctherapy (VMAT) compared with sliding window intensity-modulated radiotherapy (IMRT) for whole pelvis irradiation (WPI) of locally advanced prostate cancer (LAPC).
Authors: Riou Olivier , Regnault de la Mothe Pauline , Azria David , Vieillot Sabine , Ailleres Norbert , Dubois Jean-Bernard , Fenoglietto Pascal 
Published: February 2017

171 Background: Concurrent radiotherapy to the pelvis plus a prostate boost with long term androgen deprivation is a standard of care for LAPC. IMRT has the ability to deliver highly conformal dose to the target while lowering the irradiation of critical organs around the prostate. However, delivery time is signicantly prolonged with static gantry IMRT. VMAT is able to reduce treatment time but results concerning organ sparing are controversial when compared to static gantry IMRT. Methods: 10 patients with locally advanced prostate cancer were included in this dosimetric study. The planning target volumes (PTV) 1 was defined as the pelvic lymph nodes, the prostate and the seminal vesicles plus set up margins. The PTV 2 consisted of the prostate with set up margins. The aimed dose to PTV1 was 54 Gy in 37 fractions and to PTV2, 74 Gy in 37 fractions, in a single plan using the integrated boost method, by means of a 7 coplanar static split fields IMRT, a one arc (RA1) and a two arc (RA2) Rapidarc planification. Results: All three techniques allow a very good coverage of both PTVs with an acceptable homogeneity. Static IMRT enables a better homogeneity for PTV 2 than Rapidarc techniques. Sliding-window IMRT and VMAT permitted to maintain doses to OAR within acceptable levels with a low risk of side-effects for each organ. Nevertheless, VMAT plans result in clinically and statistically significant reduction in doses to bladder (IMRT Vs RA2: Mean dose: 50.1 ± 4.6 Vs 47.1 ± 3.9 Gy, p = 0.037), rectum (Mean dose: 44 ± 4.5 Vs 41.6 ± 5.5 Gy, p = 0.006) and small bowel (V30: 76,47 ± 14,91% Vs. 47,49 ± 16,91%, p = 0.002). Conclusions: VMAT allows for better OAR sparing as compared to sliding-window IMRT while maintining PTV coverage into acceptable levels for WPI of LAPC.
The different genetic alterations between Western and Chinese prostate cancers and the underlying mechanisms.
Authors: Mao Xueying , Coll Bastus Nuria , Boyd Lara , Yu Yongwei , Ren Guoping , Beltran Luis , Oliver R. , Young Bryan D , Berney Dan , Lu Yong-Jie 
Published: February 2017

184 Background: Prostate cancer shows a wide variation in the clinical incidence and mortality rates of different geographical regions. While it is the most common male cancer in Western countries, it is much less frequent in Asian countries. We investigated genomic changes in prostate cancers from UK and China using microarrays to determine the genetic similarities and differences as well as the underlying mechanisms. Methods: We determined genome-wide genomic alterations using Affymetrix SNP array 6.0, and evaluated data using fluorescence in situ hybridisation (FISH) and immunohistochemistry. In addition, we assess androgen induced TMPRSS2 and ERG co-localization and fusion. Microsatellite analysis was used for AR CAG repeat polymorphism in UK and Chinese population. Results: Genome-wide analysis of 32 UK and 39 Chinese samples revealed that losses of 21q22 (leading to TMPRSS2:ERG fusion) and 10q23.3 (PTEN) were at much higher frequency in Western than Chinese prostate cancers. Using FISH analysis of 160 UK and 143 Chinese samples, we showed that PTEN deletion and ERG rearrangements were at a significantly higher frequency in samples from UK than China (p<0.001 for both). We found that PTEN and ERG protein were also differentially expressed (p<0.001) in the two populations. Investigating this further, we induced TMPRSS2 and ERG gene proximity and TMPRSS2:ERG fusion in two immortalised prostate epithelial cell lines by exposure to high dose of androgen. This androgen treatment did not cause increased global DNA damage but was associated with low expression of PIWIL1, which is involved in repairing double-strand breaks. Overexpression of PIWIL1 by transfection inhibited androgen induced TMPRSS2:ERG fusion. We found that AR CAG repeat lengths, which associated with AR activity, are significantly shorter in the UK than Chinese patients (p<0.05). Conclusions: We revealed genomic differences in prostate cancer comparing the high-risk (Western) and low-risk (Chinese) populations. We further demonstrated that TMPRSS2:ERG fusion can be induced by androgen. The difference of CAG repeat length between the two populations are potentially associated with TMPRSS2:ERG fusion positive prostate cancers.
Personalizing treatment in patients with castrate-resistant prostate cancer: A study of predictive factors for secondary endocrine therapies activity.
Authors: Loriot Yohann , Massard Christophe , Albiges Laurence , Di Palma Mario , Blanchard Pierre , Bossi Alberto , Chauchereau Anne , Escudier Bernard J. , Fizazi Karim 
Published: February 2017

213 Background: Several options have recently demonstrated activity, including survival improvement, in patients with prostate cancer progressing while on androgen deprivation therapy: chemotherapy (docetaxel, cabazitaxel), sipuleucel-T, and abiraterone. There is now an urgent need to identify predictive factors of efficacy for each of these treatments to assist decision-making in pts with castrate-resistant prostate cancer (CRPC). We attempted to identify predictive factors for activity of subsequent endocrine manipulations in patients with CRPC. Methods: Patients with CRPC included in the Institut Gustave Roussy clinical trials database who received endocrine manipulations (abiraterone, ketoconazole-hydrocortisone, DES, bicalutamide) for CRPC were reviewed. The predictive role on response and progression-free survival (PFS) of a series of clinical, biological, and radiological parameters was studied (Khi-2 test for response, Logrank test and Cox model for PFS). Results: 108 patients with CRPC who participated to 5 clinical trials were identified. The median duration of prostate cancer sensitivity to ADT (defined as the time from ADT initiation to the outset of castrate-resistance) was 16 months (range: 0–118 months). Timing of endocrine manipulation (before vs after docetaxel-based chemotherapy), presence of non-bone visceral metastases, the type of progression (clinical vs radiological), Performance Status, and PSA doubling time did not predict for response or PFS. In contrast, the previous duration of prostate cancer sensitivity to ADT (classified as ≥16 months and <16 months) significantly and strongly predicted for both PSA response (58% vs 18%, p=0.01) and PFS (median PFS rates: 5 months (95%CI: 3.46–6.53) and 3 months (95%CI: 2.10–3.89) p<0.043). Conclusions: A previous duration of prostate cancer sensitivity to ADT ≥16 months is the only significant predictive factor for efficacy of subsequent endocrine manipulations in patients with CRPC. This parameter shall be integrated into the decision-making process for these patients.
Return-to-work after radiotherapy for prostate cancer.
Authors: Sveistrup Joen , Petersen Peter Meidahl , Mortensen Ole Steen , Engelholm Svend Aage 
Published: February 2017

218 Background: Returning to work following cancer treatment is a sign of recovery. The purpose of this study was to determine how many patients return to work following definitive intensity-modulated radiotherapy for prostate cancer (PCa). Methods: The Danish DREAM-database contains information on all social benefits paid out to Danish citizens. The data are recorded prospectively every week. Based on the DREAM-database it is possible to assess whether a patient is working, on sick leave, or retired. Data on 410 of the 451 Danish citizens, treated with definitive intensity-modulated radiotherapy for PCa at our center between January 1 2006 and May 1 2010, were obtained from the DREAM-database one year prior to radiotherapy, at the start and at the end of the radiotherapy, and finally one year after radiotherapy was completed. The median age was 66 (age range, 49–76). Patients were divided into five different categories. The categories were “Working or unemployed”, “Sick leave”, “Disability pension”, “Retirement” and “Dead”. Results: The results are shown in the table. Nearly 30% of the patients are working or available for work one year prior to the radiotherapy. This number is reduced to about 12 % at the time of both the start and the end of the radiation treatment. One year after treatment nearly 20% are working. Conclusions: This study shows that a substantial proportion of patients return to work following definitive radiotherapy for PCa. This indicates that the treatment in many cases does not affect the patients’ ability to work. Further research should be on why some patients stop working after completion of definitive radiotherapy for PCa. [Table: see text]
Assessment of the American Joint Committee on Cancer (6th and 7th editions) for clinically localized prostate cancer and comparison to the National Comprehensive Cancer Network risk stratification method.
Authors: Buyyounouski Mark K , Zaorsky Nicholas G. , Li Tianyu , Devarajan Karthik , Horwitz Eric M. 
Published: February 2017

23 Background: The purpose was to compare the prognostic value of the AJCC staging version 6 (v6), version 7 (v7), and the risk-stratification model of the NCCN. Methods: 2,469 men (1989-2006) with clinical T1-4, N0/X-N1, M0 prostate cancer received definitive RT +/- ADT (median follow-up: 70 months). The NCCN grouping was: low-risk included T1-T2a, GS < 7, and PSA < 10 ng/mL; intermediate-risk included T2b-2c, GS = 7, and PSA 10 – 20 ng/mL; high-risk included T3, GS 8, and PSA > 20 ng/mL. The Benjamini and Hochberg adjustment was used to compute the false discovery rates in order to adjust for multiple comparisons. Results: There was a migration of stage II patients to stage I with version 7 (Stage I increased from 1% to 38%, while Stage II decreased from 91% to 55%). Pair-wise comparisons of Kaplan-Meier estimates of BF, DM, PCSS, and OS between stages were not statistically significant for AJCC v6 with one exception (PCSS: II vs III). On the other hand, 16/24 (67%) of comparisons were significant with AJCC v7. For NCCN, 9/12 (75%) of comparisons were significant, including all comparisons for OS. Concordance probability estimate (CPE) and standard error (SE) analysis showed uniform and significant improvement in the predictive power of AJCC v7 versus AJCC v6 for all outcomes. CPE±SE values for AJCC v6 versus AJCC v7 was .51±.009 vs .59±.02 for BF, .54±.02 vs. .70±.05 for DM, .57±.009 vs. .76±.007 for PCSS, and .52±.006 vs. .57±.01 for OS. There was further, albeit modest improvement with the NCCN method. CPE±SE values for AJCC v7 versus NCCN was .59±.02 vs. .59±.02 for BF, 0.70±.05 vs. 0.72±.05 for DM, .76±.007 vs. .80±.01 for PCSS, and .57±.01 vs. .57±.01 for OS. Conclusions: AJCC v7 is a major improvement over AJCC v6 because it better distributes patients among the stages and is more prognostic. Further improvements are needed as the majority of men (55%) are Stage II and the sub-stratification into IIA and IIB was not prognostic. The NCCN model is superior to the AJCC v7 and remains the preferred method for risk-based clinical management of prostate cancer with RT +/- ADT.
Effect of PEDF on survival and the in vivo antitumor activities of low-dose chemotherapy in castration-refractory prostate cancer.
Authors: Nelius Thomas , Pardue Natalie , Gillen Jessica , Rinard Katherine , Hirsch Jennifer , Cobos Everardo , Reynolds C. Patrick , Filleur Stephanie 
Published: February 2017

237 Background: The development of metronomic/low dose of conventional chemotherapeutic drugs have recently showed great promise in the treatment of castration-refractory prostate cancer (CPRC). Pigment Epithelium-Derived Factor (PEDF) is a natural angio-inhibitor which is down-regulated in prostate cancer. We have previously demonstrated that the over-expression of PEDF in human CRPC PC3 cells decreased tumor growth in vivo. In the present study, we further validated PEDF anti-tumor properties in the highly metastatic CRPC LNCaP-derivative CL1 cells. We also hypothesized that PEDF may enhance the cytotoxicity effects of low dose docetaxel (Doc) and cyclophosphamide (CTX) chemotherapies in vivo. Methods: Human PC3 and CL1 cell lines were genetically modified to stably express the fluorescent DsRed Express protein with PEDF. Resulting cells were characterized in vitro for PEDF expression by western blot and, for proliferation by growth curves and clone formation in matrigel. PEDF anti-tumor effects were assessed on established s.c. xenografts in mice treated with Doc (5mg/kg ip every 4 dy, 1mg/kg ip daily for 10 days, 0.5mg/kg every other day), CTX (10-20mg/kg in the drinking water) or placebo. Survival studies were performed by injecting CL1 cells with 50nM hrPEDF or carrier control into the left lobe of the dorsal prostate of anesthetized mice. Results: We showed that PEDF inhibits the proliferation and induces the differentiation of all CPRC cells tested in vitro. Similarly, PEDF expression decreases by 85% and 70% the development of s.c. PC3 and CL1 tumors, respectively. In the survival study, we found that all control animals die within 61 days after surgery while 50% of PEDF-pretreated animals were still alive. Most importantly, we demonstrated that PEDF enhances the cytotoxicity effects of low dose chemotherapy on established tumors (best Doc dose: 1mg/kg for PC3 and 5mg/kg for CL1; best CTX dose: 10mg/kg for PC3 and CL1). Conclusions: These data reinforce the significance of PEDF as a potential new target for the treatment of advanced prostate cancer. It also emphasizes PEDF as a promising new agent to enhance the anti-tumor efficacy of low dose Doc and CTX chemotherapies.