bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dependence of intrafraction prostate motion within the pelvis on fraction duration during whole pelvic intensity modulated arctherapy (IMAT) versus dynamic IMRT.
Authors: Lescut Nicolas , Martin Etienne , Maingon Philippe , Quivrin Magali , Mirjolet Celine , Naudy Suzanne , Petitfils Aurelie , Crehange Gilles 
Published: February 2017

190 Background: To compare the 3-dimensional intra-fraction variations of prostate position within the pelvis with whole-pelvic fixed-field intensity-modulated radiation therapy (IMRT) vs. intensity-modulated arc therapy (IMAT) in high-risk prostate cancer. Methods: Fifteen PCa patients underwent whole pelvic radiotherapy using either dynamic IMRT with a sliding window technique (n= 8) or IMAT (n= 7). All the patients had a kV cone-beam computed tomography (CBCT) before and immediately after each fraction of IMRT or IMAT. Intra-fraction motions of the prostate were determined using a 2-step procedure performed on each pre- and post-treatment imaging: 1) planning CT and CBCT were matched on bony structures after automatic semi-rigid fusion alongside the 3 axis (x, y, z), 2) planning CT and CBCT were matched on the prostate with respect to intra-prostatic markers: xsoft, ysoft, zsoft. The position of the prostate within the pelvis for each pre- and post-treatment study points was defined as xpros= (xbone – xsoft), ypros= (ybone – ysoft) and zpros= (zbone – zsoft). Rectum and bladder were outlined on each CBCT with the aim to assess changes in rectal or vesical repletion during each fraction. Organ distension was assessed by measuring the average rectal cross-sectional area (rCSA; defined as the rectal volume divided by length), and the area of the bladder when evaluated 2.5cm above the prostate base (A-blad) on pre- and post-treatment CBCT. Results: Two hundred and ninety four CBCT were reviewed for this analysis. The average fraction duration was shorter with IMAT than with IMRT (4’49’’, vs. 11’00’’, p< 0.001). During fractions of IMRT the prostate showed statistically significant shifts in the longitudinal (p= 0,049) and lateral (p=0,013) axis while it was not statistically significant during fractions of IMAT. Intra-fraction rCSA increased neither during IMAT nor IMRT whereas A-blad increased only during fractions of IMRT but with no correlation with prostate displacements. Conclusions: The prostate moves within the pelvis during an IMRT course which could lead to a greater daily geographic miss when compared to the IMAT technique.
A phase II study of linsitinib (OSI-906) in patients with asymptomatic or mildly symptomatic (non-opioid requiring) metastatic castrate resistant prostate cancer (CRPC).
Authors: Garcia Jorge A. , Elson Paul , Cooney Matthew M. , Tyler Allison Janine , Rezash Victoria , Borden Ernest C. , Dreicer Robert 
Published: February 2017

197 Background: Novel agents capable of blocking AR ligand independent pathways responsible for the development of CRPC are needed. IGF-1R and its ligands (IGF-1/IGF-2) play a key role in regulating growth, resistance to apoptosis, and invasion in PCa. IGF-1R is overexpressed in PCa and mediates resistance to ADT. OSI-906 is a small molecule potent dual inhibitor of IGF-1R and insulin receptor TK activity. To determine the activity of OSI-906 in men with CRPC a Simon two-staged phase II study was conducted. Methods: Men with asymptomatic or mildly symptomatic Met CRPC were eligible. ECOG 0-1, adequate organ function, and no prior chemotherapy for CRPC were required. Pts received OSI-906 at 150mg orally twice daily on a 28-day cycle. Endpoints included PSA response at 12 wks, safety, RECIST-defined response, time to PSA progression, and OS. Correlative studies explored the impact of OSI-906 on AR signaling (androstenedione, DHEA, DHEA-sulfate, p-IGF-1R, p-IR), markers of PD (TGF-b1, IL-6, TNF-a, MCP-1), and CTC and CECs. Results: To date 18 pts have enrolled and completed 12 wks of therapy. Median age 68 (55-78); Median pre-treatment PSA was 55.23 (range 2.46-277.60); 41% of pts had bone-only disease, 29% soft-tissue only and 29% had both. Although transient PSA declines were noted, 17/18 pts discontinued therapy sec PSA progression. RECIST-defined SD was observed in 8 pts. Pts received a median of 3 cycles of therapy (range 2-6+). Most common G1/2 AEs included AST/ALT changes observed in 41 and 18% of patients respectively, fatigue (59%); prolong QT interval (35%) and nausea/vomiting (35%). No significant change in the number of CTC and CEC counts was observed. An association between pre-treatment PSA and pre-treatment CTC was observed (Spearman r=0.49, p=.04). No correlation between CTC changes and PSA progression was observed .Evaluation of other molecular markers of PD is underway. Conclusions: Treatment with OSI-906 is safe. No PSA responses or changes in CTC/CECs were noted. Markers of PD might help elucidate potential mechanisms of escape to this alternative pathway in CRPC. OSI-906 plus an AA might provide synergistic activity in this setting. Clinical trial information: NCT01533246.
Long-term responders to enzalutamide (ENZA) during the phase III AFFIRM trial: Baseline characteristics and efficacy outcomes.
Authors: Fleming Mark T. , Scher Howard I. , Fizazi Karim , Taplin Mary-Ellen , Forer David , Hirmand Mohammad , De Bono Johann Sebastian 
Published: February 2017

20 Background: ENZA, an oral androgen receptor inhibitor, was shown to significantly increase overall survival by 4.8 mo (P <0.001, HR 0.63) vs placebo (PBO) in AFFIRM, a phase III trial in patients (pts) with castration resistant prostate cancer (CRPC) post- docetaxel. Here we report the baseline characteristics and efficacy outcomes of long-term responders (LTR, ≥12 months on ENZA) in the AFFIRM trial. Methods: Pts were randomized 2:1 to ENZA 160 mg/day or PBO. The primary endpoint was overall survival (OS). The study was stopped at the pre-specified interim analysis (520 events). Pts in the ENZA group were allowed to continue on ENZA post unblinding. The LTR group was defined by Aug 2012 data cut-off. Efficacy data are from interim analysis data cut-off from Sep 2011. Results: 35% (276/800) of the ENZA group were on therapy for ≥ 12 months; 22% (174/800) for > 18 months. Comparing the LTR subgroup to the all ENZA group, the LTR subgroup had been living with prostate cancer longer (7.9 vs 5.9 yrs) and had lower disease burden at baseline (Table). Pts in the LTR subgroup had improved efficacy outcomes compared to all ENZA group. Of note, 50% PSA response was 87% in LTR subgroup vs 54% in the all ENZA group. Results are preliminary, updated results will be presented. Conclusions: 35% of pts in AFFIRM received ENZA for ≥12 months. Compared to the all ENZA group, LTR pts had less disease burden at baseline and had improved efficacy outcomes. Clinical trial information: NCT00974311. [Table: see text]
Current status and outcomes of salvage radiotherapy for patients with PSA recurrence after prostatectomy: A JROSG surveillance study.
Authors: Mizowaki Takashi , Aoki Manabu , Nakamura Katsumasa , Yorozu Atsunori , Kokubo Masaki , Karasawa Katsuyuki , Kozuka Takuyo , Nakajima Nobuaki , Sasai Keisuke , Akimoto Tetsuo 
Published: February 2017

207 Background: Salvage radiotherapy (S-RT) for patients with prostate cancer who developed PSA failure after radical prostatectomy is widely applied. However, current status of this approach in Japan has not been surveyed so far. The aim of this study was to reveal the present conditions and outcomes of S-RT for Japanese patients with biochemically recurrent prostate cancer. Methods: Clinical data of the S-RT was gathered by sending a questionnaire to participating facilities to the Japanese Radiation Oncology Study Group (JROSG). The S-RT was defined as external-beam radiotherapy delivered to the prostate bed to patients with prostate cancer who eventually developed PSA failure, although their PSA value had once reached <0.2 ng/ml after prostatectomy. In addition, the interval between prostatectomy and the S-RT should essentially be six months or longer. PSA failure-free survival (PFFS) and clinical failure-free survival (CFFS) was calculated by the Kaplan-Meier estimation. Results: 371 cases were registered from 38 facilities. Among them, hormonal therapy was combined with S-RT in 151 patients. In 3 cases, chemotherapy was combined before or after the S-RT. The rests of the cases were treated by S-RT alone. However, prognostic information was insufficient in 28 cases, and PSA nadir was >0.2 ng/ml in 3 cases. Therefore, outcome studies were conducted in the remaining 186 cases. The median age was 67 years old. The nadir value of the PSA after prostatectomy and the PSA value at the initiation of S-RT were 0.0135 ng/ml and 0.292 ng/ml, respectively. The median period between prostatectomy and the S-RT was 18.6 months. Median follow-up period was 58 months. The 5-year PFFS and CFFS were 50.1% (95%CI: 42.8 – 57.9) and 90.1% (95%CI: 86.4 – 95.7), respectively. PFFS was significantly superior in patients with PSA values <= 0.3 ng/ml at the initiation of S-RT than those of PSA values > 0.3. (57.5% vs. 40.5%, p = 0.027) Conclusions: In Japan, hormonal therapy was combined with S-RT in about 40% of the cases. The 5-year PFFS and CFFS rates of cases treated by S-RT alone were 50.1% and 90.1%, respectively. A PSA value of 0.3 was significant cut-off point for predicting PFFS.
High-dose-rate brachytherapy combined with external beam radiotherapy for localized prostate cancer: Correlation between clinical and dosimetric parameters and the incidence of rectal bleeding.
Authors: Kariya Shinji , Yamasaki Ichiro , Ashida Shingo , Tamura Kenji , Shuin Taro , Nishioka Akihito , Ogawa Yashuhiro 
Published: February 2017

213 Background: Several investigators have advocated that the alpha/beta ratio for prostate cancer is atypically low, and that hypofractionated radiotherapy or high-dose-rate brachytherapy (HDR-BT) regimens using appropriate radiation doses are expected to improve the local control rate for localized prostate cancer. However, the increase in the total biological effective dose (BED) may cause increased severity and incidence of normal tissue complications. The purpose of this study was to investigate what clinical and dosimetric factors affected the incidence of rectal bleeding after HDR-BT combined with external beam radiotherapy (EBRT). Methods: A total of 143 patients with localized prostate cancer underwent HDR-BT combined with EBRT. The fractionation schema for HDR-BT and EBRT was prospectively changed: 9 Gy x 2 + 2 Gy x 20 (BED1.5 = 219 Gy, BED3 = 139 Gy) in 57 patients (Group 1); and 9 Gy x 2 + 3 Gy x 13 (BED1.5 = 243 Gy, BED3= 150 Gy) in 86 patients (Group 2). Median follow-up was 59 (range, 36 – 94) months. The toxicities were graded based on the National Cancer Institute-Common Terminology Criteria for Adverse Events v3.0. Results: Sixteen (11.2 %) and one patients developed Grade 2 and 3 rectal bleedings, respectively. There were no significant differences between Group 1 and Group 2 in the incidence of Grade 2 and 3 rectal bleedings (12.3% and 11.6%, respectively). Grade 2 and 3 rectal bleedings occurred much more in the patients receiving the antiplatelet therapy (AT) (19.4%) than those without a history of AT (9.8%) and in the patients with diabetes mellitus (DM) (37.5%) than those without DM (10.4%). However, neither AT nor DM were risk factors in univariate analysis. Regarding dosimetric factors, V75 > 2cc, V90 > 0.2cc, D2 > 7 Gy, and D1 > 7.4 Gy were statistically-significant risk factors. In multivariate analysis, DM was the only statistically-significant risk factor. Conclusions: BED escalation could be performed without severe rectal bleeding in HDR-BT combined with EBRT. V75 > 2cc, V90 > 0.2cc, D2 > 7 Gy, D1 > 7.4 Gy, and DM were risk factors for the incidence of rectal bleeding in HDR-BT combined with EBRT. Clinical trial information: 18-9.
Salvage brachytherapy for prostate bed recurrence following radical prostatectomy.
Authors: Smith Kristin , Ciezki Jay P. , Stephans Kevin L. , Reddy Chandana A. , Klein Eric A. 
Published: February 2017

218 Background: Approximately 10% of patients who undergo a radical prostatectomy (RP) for localized prostate cancer subsequently experience a local recurrence. A small percentage of these patients present with prostate bed nodules (PBN). We present here, a case series of 12 patients treated with low dose rate brachytherapy (BT) for a PBN post RP. Methods: All 12 patients had biopsy confirmed cases of recurrent adenocarcinoma in the prostatic bed. At the time of PBN diagnosis, 2 patients had received EBRT, 2 patients had received ADT, and 1 patient had undergone HIFU. Patients were confirmed to have a negative CT and bone scan prior to salvage BT. All patients received salvage BT with I-125 prescribed to 144 Gray. Results: The median interval between RP and BT was 8 years (range 0.5- 17.9), median PSA prior to BT was 4.53 ng/ml (range 0.55-15.2), and the median age was 69 (range 59-86). Forty-two percent of patients had a PBN Gleason score of 8, 33% had a score of 7, and a score was not reported for 25% of patients due to prior EBRT or ADT use. The median follow up for this series is 26.5 months (range 1-69). At the time of this analysis, 10 patients were evaluable for biochemical failure (bF) (nadir+2) and distant metastases (DM). The one and two year rates of bF were 0% and 52%. There was no association between pre-BT PSA and bF, nor between pre-BT Gleason score and bF. Two patients subsequently developed DM at 17 months and 55 months after BT. The pelvic lymph nodes were the site of DM for both patients. The median PSA velocity post BT was -0.120 ng/ml/yr (range -1.404- 9.096). Five patients had a negative PSA velocity at last follow-up, while 4 had an increasing PSA velocity. Velocity could not be defined for 3 patients (insufficient PSA n=2, ADT n=1). To date, no gastrointestinal or urinary toxicities have been noted. Conclusions: Brachytherapy as a salvage treatment for a PBN appears to be well tolerated. The rates of bF and DM following salvage BT are comparable to those of salvage EBRT for this patient population. Intermediate-term biochemical control was attained in a sub-set of patients with declining PSA at last follow-up.
Relationship of overall survival and the frequency of performing transrectal ultrasound-guided biopsy of the prostate in those patients with low-risk tumors electing active surveillance.
Authors: Buethe David D. , Russell Christopher , Yue Binglin , Lin Hui-Yi , Pow-Sang Julio M. 
Published: February 2017

238 Background: Limited derived benefit from definitive treatment has been observed with respect to prostate cancer−specific mortality (PCSM) in those low−risk disease and only small absolute risk reductions in both overall PCSM and incidence of metastasis have been demonstrated. Thus, active surveillance (AS) strategies have been adopted to monitor for disease progression with intent for intervention at time of disease reclassification. Yet, the timing and frequency of surveillance remain without evidence-based standardization. We assessed the relationship between the frequency of surveillance prostate biopsies and the oncologic outcomes in those patients with low−risk prostate cancer (CaP) managed by AS. Methods: An IRB approved retrospective chart review identified 114 patients placed on AS for their CaP between November of 1997 and November of 2000. Of those, 96 patients meet study inclusion criteria mandating a Gleason sum of < 7, tumor presence in < 4 sextets, involvement of <50% of any single biopsy core. Eligible patients were surveyed by serum PSA, DRE, and surveillance TRUS−guided biopsies at physician determined intervals. Results: At diagnosis, the mean age was 70.3 (SD±5.3) years with a mean PSA value of 8.2 (SD±8.2) ng/dL. While on AS, patients underwent a median of 3.5 (SD±2.02) TRUS−guided biopsies; at a frequency approaching 1 biopsy every 18 months. At a median follow−up of 134.8 months (95%CI: 114.5, 148.7), multivariate analysis found more frequent prostatic biopsy acquisition to be inversely associated a worse prognosis with respect to both progression−free (p<0.0001) and overall survival (p=0.0002). Both progression−free (p<0.0001) and overall survival (p=0.0207) were progressively shorter as the interval between biopsies declined from greater than 2 years, to 1−2 years, and then less than 1 year. Conclusions: No survival advantage was achieved by frequent re−biopsy of the prostate. Patients biopsied more frequently were paradoxically found have poorer survival outcomes.
Genomic characterization of metastatic urothelial carcinoma.
Authors: Bambury Richard M. , Riester Markus , Bellmunt Joaquim , Stack Edward C. , Werner Lillian , Park Rachel , Iyer Gopa , Loda Massimo , Kantoff Philip W. , Michor Franziska , Rosenberg Jonathan E. 
Published: February 2017

247 Background: The genetic profile of primary urothelial carcinoma (UC) has been well documented but no reports analyze specific chromosomal alterations in metastatic disease. We performed molecular inversion probe array (MIP) analysis to compare chromosomal gains or losses in metastatic and primary UC samples. Methods: 33 samples of metastatic UC and 30 primary samples were analyzed from 48 patients (pts), of which paired primary and metastatic tissue was available for 14 pts. DNA from all samples was subjected to molecular inversion probe array analysis to identify focal areas of copy number gain (CNG) or loss (CNL). We focused this analysis on 21 genes from signaling pathways known to be of interest in UC (Table). CNG or CNL was defined as a log2 copy number ratio ≥ 0.8 or ≤ -0.8. GISTIC 2.0 was used to identify significantly altered regions. Results: In the loci analyzed, there were significantly more alterations in metastases than primary samples (8.4% vs 4.3% p=0.002). In particular, there was a significantly higher frequency of E2F3CNG in metastases (27% vs 7% p=0.046). There was frequent discordance in alterations when comparing primary and metastatic tissue from the same patients: 7 of 14 pts harbored potentially oncogenic CNG/CNL in their metastases that were not present in the primary. Conclusions: More alterations in UC-relevant genes were identified in metastases compared with primary tumors, in keeping with the multistep model of cumulative genetic change in cancer progression. More frequent CNG of the E2F3 gene was noted and may represent a mechanism of UC progression. Frequent discordance in alterations between primaries and metastases may be of significant clinical relevance in the future when selecting patients for appropriate molecularly targeted therapy. [Table: see text]
Impact of the USPSTF D recommendation: Early assessment of referrals for elevated PSA and prostate biopsies in a LUGPA following statement revision.
Authors: McGinley Kathleen F. , Brown Gordon Andrew 
Published: February 2017

25 Background: In October 2011, the U.S. Preventative Services Task Force (USPSTF) posted for public comment the draft of their recommendation against prostate cancer screening. Extensive media coverage and discussion within the medical community ensued. The USPSTF released their formal statement of a D recommendation in May 2012. While the potential implications of the USPSTF recommendation upon prostate cancer screening will take years to manifest, the early impact of their recommendations upon the market is evaluable. Methods: The electronic medical record of a large urology group practice composed of 32 physicians was queried for two variables: the number of referrals for an elevated PSA and the number of individuals who underwent a prostate biopsy. A control period of October 2010-September 2011 was selected and compared to October 2011-September 2012, the twelve month period beginning with release of the USPSTF draft against prostate cancer screening. Results: From October 2010 to September 2011, 28698 patients were evaluated for an elevated PSA by 32 urologists; from October 2011 to September 2012, 25075 patients were evaluated by the same number of physicians, a difference of 12.6% following release of the USPSTF recommendations. From October 2010 to September 2011, 2465 patients underwent a prostate biopsy; from October 2011 to September 2012, 1989 had a biopsy, a difference of 19.3%. Conclusions: A marked decrease in the number of patients referred to a large urology group practice for evaluation of an elevated PSA, and an even greater decrease in the number of prostate biopsies performed, occurred in the 12 months following release of the USPSTF recommendations against prostate cancer screening.
Progression-free survival as an endpoint for clinical trials in first-line metastatic urothelial cancer.
Authors: Galsky Matt D. , Krege Susanne , Lin Chia-Chin , Hahn Noah M. , Ecke Thorsten , Moshier Erin L. , Sonpavde Guru , Godbold James H. , Oh William K. , Bamias Aristotelis 
Published: February 2017

251 Background: Advances in the first-line treatment of metastatic urothelial cancer (UC) have proven elusive. The lack of appropriate intermediate endpoints to screen the activity of novel regimens may be a barrier to progress, particularly in this disease state characterized by relatively high response rates but short response durations. Progression-free-survival (PFS) at fixed time points may overcome several of the limitations of response rate-based endpoints, but would be further supported by establishing benchmarks and demonstrating a correlation between PFS and overall survival (OS). Methods: Data were pooled from eight phase II and III trials evaluating first-line cisplatin-based chemotherapy in metastatic UC. Landmark analyses for progression at 3, 6, and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS. Results: 545 patients were included in the analysis. The median PFS was 7.75 months (95% CI, 7.06, 8.18) and the median OS was 12.35 months (95% CI, 10.97, 13.44). The results of the landmark analysis, adjusted for performance status ≥ 1 and presence of visceral metastases, is shown in the Table. By using the Fleischer model, the estimated correlation between PFS and OS was 0.86 (bootstrap standard error 0.001, 95% CI 0.83, 0.89). Conclusions: PFS at 3, 6, and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy. This analysis provides benchmarks, and support, for the use of PFS as an endpoint for phase II trials screening the activity of novel regimens as first-line treatment for metastatic UC. [Table: see text]