bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of circulating tumor cells (CTCs) in biochemical recurrence (BR) of prostate cancer.
Authors: Aragon-Ching J. B. , Simmens S. J. , Hendricks F. , Andrawis R. , Frazier H. , Jarrett T. , Patierno S. R. , Siegel R. S. 
Published: February 2017

60 Background: CTCs have an established role in the prognosis of metastatic prostate cancer. Little data exists regarding the role of CTCs in BR of prostate cancer. The aim of this study was to determine whether there is a correlation between the number of CTCs in men with BR with varying prostate specific antigen (PSA) and PSA doubling time (PSADT) categories. Secondary endpoints looking at correlation of the CTCs with clinical or laboratory factors (Gleason scores, testosterone, hemoglobin, alkaline phosphatase, BMI, imaging results) will also be assessed. Methods: BR was defined as patients (pts) who have undergone primary treatment with prostatectomy or radiation or both, with rise to >/= 0.2 from a prior undetectable level for prior prostatectomy or > 2 mg/dl rise from post-nadir radiotherapy. The study was powered to detect a Pearson correlation of .46 with a sample size of 36. Eleven of planned accrual goal of 36 pts were enrolled from May to September 2010. PSADT was obtained and correlated with the CTC values, categorized as PSADT of < 3 months, 3-14.9 months and > 15 months. CTCs were evaluated in 7.5 mL of peripheral blood using the CTC CellSearch test. Results: The median age for 11 patients was 75 y/o (range: 57-91) with a median PSA of 1.6 ng/mL (range 0.2-6.5) and testosterone levels of 309 ng/dL (range: 31–471). Gleason scores were 8 (n=1), 7 (n=5), 6 (n=2), 5 (n=3). Prostatectomy was the primary treatment in 6 pts, radiotherapy in 5 pts and Cyberknife in 1 pt. Median hemoglobin was 12.43 g/dL, BMI was 26.79 and alkaline phosphatase was 69 IU/L. PSADT varied between 3 to 55 months. All pts accrued had 0 CTC levels. The latter result translates into a 95% confidence interval upper bound of approximately .27 for the proportion of patients in this population who have non-zero CTC levels. Conclusions: Prostate cancer pts with BR have negative blood CTCs and does not appear to correlate with PSA or PSADT. However, the limited number of patients precludes sufficient interpretation at this time and further accrual is ongoing. The absence of CTC levels in this patient population, if supported through further data collection, could emerge as an important unanticipated finding from this study. Supported by IRG-08-091-01 from ACS to GWU Cancer Institute. No significant financial relationships to disclose.
High toxicity in patients receiving adjuvant docetaxel plus hormone treatment after radical radiotherapy for high-risk prostate cancer: A preplanned safety report of SPCG 13 trial.
Authors: Kellokumpu-Lehtinen P. , Hjelm-Eriksson M. , Thellenberg-Karlsson C. , Astrom L. , Franzen L. , Marttila T. , Taalikka M. , Ginman C. 
Published: February 2017

63 Background: In two randomized trials a survival benefit has been shown for docetaxel (T) in metastatic, hormone refractory prostate cancer PrCa). In order to increase the recurrence-free survival and overall survival with adjuvant treatment we conducted a randomized trial using T in patients (pts) with high risk PrCa after radical radiotherapy (RT). Methods: Between May 2007 and April 2009 100 pts with PrCa Gleason score (GS) 7 (4+3) and cT2 tumors with PSA >10 to <70 ng/mL or cT2 tumors with GS 8-10 or any cT3 tumors without metastases were randomized between surveillance (S) or six courses of T 75 mg/m2 q21d at the end of RT. Neoadjuvant + adjuvant LHRH-treatment for 9 mo was mandatory. The defined end-point is PSA relapse (ASTRO-RTOG guidelines). The groups were well balanced; mean age 65 vs 66 years, ECOG (0/1, %) 90/10 vs 90/10; time from diagnosis 262 vs 270 days, GS (6-7/8-10, %) 60/40 vs 44/56; tumor stage (T2/T3, %) 26/74 vs 28/72 in groups T vs S, respectively. The mean PSA of the 100 pts at the time of diagnosis was 21.9 ng/mL and the nadir PSA after RT was 0.25 ng/mL. By September 2010 227 out of 378 pts have been randomized to this SPCG 13 trial, NTC 006653848. Results: During T treatment Grade (G) 3 adverse event (AEs) occurred in 15 pts (30%) and G 4 AEs in 30 pts (60%) mainly due to bone marrow toxicity, which was higher than expected; neutropenia G 3-4 in 72% of the pts. Febrile neutropenia in 24% of the pts, neutropenic infection in 10% the pts and G3 infection without neutropenia in 4% of pts was recorded. Nonhematological G 3 AEs (pts) were rare; anorexia (1), diarrhea (3), fatigue (5), mucositis (1), nausea (1) and pain (1). Other severe SAEs related to T were pulmonary embolism and renal failure. However, only three pts stopped T before 6 cycles were completed due to toxicity. No deaths have occurred. In the S arm only one patient experienced G 3 toxicity (pain) 12 weeks after the randomization. Conclusions: Adjuvant T chemotherapy after RT has a higher frequency of neutropenia than previous studies on pts with metastatic disease, but very similar to the SPCG 12 trial of adjuvant T after surgery. Otherwise the treatment was quite well tolerated. [Table: see text]
Evaluation of a prostate brachytherapy technique designed to reduce short- and long-term urinary dysfunction: 5-year results of a multi-institutional comparative cohort study.
Authors: Talcott J. A. , Zietman A. L. , Kaplan I. D. , Clark J. A. , D'Amico A. V. 
Published: February 2017

70 Background: To evaluate a novel prostate brachytherapy technique designed to reduce short- and long-term urinary dysfunction by sharply reducing periurethral prostate radiation (XBT), we compared urinary outcomes of XBT patients to those of 2 groups treated with standard technique (SBT) in a prospective 5-year cohort study. Methods: We surveyed newly diagnosed, untreated patients patients with clinically localized prostate cancer before brachytherapy to gather demographic, clinical and quality of life information, with follow-up at 1, 3, 12, 24, 36, 48 and 60 months after treatment. XBT patients were treated at Brigham and Women's Hospital. SBT was given at Beth Israel-Deaconess or Metrowest Hospital, which used the same technique, or at Massachusetts General Hospital. Results: Of 263 enrolled patients who completed at least 3-month follow-up, including 73 XBT patients and 190 SBT patients, 99 at 1 site (SBT1) and 91 at the other (SBT2), 167 (63%) had completed 5-year follow-up as of September 2010. XBT patients were younger and reported more baseline urinary obstruction/irritation, but the treatment groups were otherwise similar before treatment. Urinary obstruction/irritation was increased for 24 months. XBT patients reported lower increases which resolved earlier. SBT2 patients initially reported greater urinary dysfunction than SBT1 patients, but the problem resolved after changing technique to better localize the urethra. Urinary incontinence appeared to rise at 60 months after SBT but not XBT. Of patients who reported complete pretreatment urinary control, 33% of SBT vs. 15% of XBT patients reported some incontinence (p=0.08). Conclusions: Sharply reduced periurethral radiation suppresses post-treatment increases in urinary obstruction/irritation and may reduce long-term urinary incontinence. No significant financial relationships to disclose.
Percentage of positive biopsy cores to predict distant metastasis of prostate cancer after definitive radiation therapy.
Authors: Huang J. , Kestin L. L. , Vicini F. A. , Williams S. G. , Ye H. , McGrath S. D. , Ghilezan M. , Martinez A. 
Published: February 2017

80 Background: To assess the prognostic value of percentage of positive biopsy cores (PPC) and perineural invasion (PNI) in predicting clinical outcome following radiotherapy (RT) for prostate cancer. Methods: One thousand and fifty-six patients with clinical stage T1-T3 N0 M0 prostate cancer, who had ≥ 4 biopsy cores sampled and complete biopsy core data available, were treated with either adaptive image-guided RT (median 75.6 Gy, n=387), low-dose EBRT (median 66.6 Gy, n=393), or EBRT and high-dose rate brachytherapy boost (n=276) at William Beaumont Hospital (1993-2004). Neoadjuvant and/or adjuvant androgen deprivation (AD) were given to 253 patients (24%). Multivariate cox regression analysis included PPC, gleason score, PSA, T stage, PNI, RT dose, androgen deprivation, and age. Biochemical failure (BF) was scored according to the Phoenix definition. Clinical failure (CF) was defined as any locoregional recurrence (LRR) or distant metastasis (DM). Median follow-up was 7.6 years. Results: Median cores sampled was 7, median PPC was 33%, and 18% had PNI. On univariate Cox regression, both PPC and PNI were predicators of biochemical failure and clinical failure (all P<0.05). On multivariate Cox regression, PPC, either as continuous or categorical variable, remained an independent predicator of BF, CF, DM, cause-specific survival, and overall survival (all P<0.05). PPC of >50% was associated with significantly higher DM (HR 4.01, 95% CI 1.86-8.61), and its independent predicative value remained significant whether AD was given or not (all P<0.05). Combining ≤50% vs ≥50% PPC with NCCN risk group stratification demonstrated added prognostic value of DM for intermediate-risk (HR 5.44, 95% CI 1.78-16.6) and high-risk groups (HR 4.39, 95% CI 1.70-2.84), with or without AD (all P<0.05). On multivariate Cox regression, PNI was an independent predicator of LRR only (HR 2.51, 95% CI 1.18-5.33). Conclusions: PPC is an independent and powerful predicator of DM for intermediate- and high-risk prostate cancer, regardless the use of AD. It should be considered for risk stratification and when designing for future trials testing adjuvant treatment after definitive RT for prostate cancer. No significant financial relationships to disclose.
Brachytherapy as salvage treatment for local nodular recurrence of prostate cancer.
Authors: Kumar A. M. , Traudt K. , Ciezki J. P. , Reddy C. A. , Klein E. A. 
Published: February 2017

86 Background: Men diagnosed with adenocarcinoma of the prostate treated with radical prostatectomy (RP) have a 10% risk of developing local recurrence within 10 years. While the majority of these recurrences are biochemical failures with no foci of disease, we report on a series of 7 patients who had nodular recurrences in the post-surgical bed and subsequently underwent low-dose rate (LDR) brachytherapy as salvage therapy. Methods: Patients who were initially treated with RP and subsequently with salvage LDR I-125 brachytherapy for a nodular recurrence were included in this series. All patients failed biochemically within 10 years of RP and received no other adjuvant or salvage treatment by choice. Nodular recurrences were biopsy confirmed adenocarcinoma, and patients had no evidence of nodal or distant metastasis on imaging or bone scan. All patients consented to salvage with LDR brachytherapy. Follow up post-salvage was at least every 6 months with a serial PSA. Results: Seven patients underwent salvage LDR brachytherapy with median age of 74 (range 63-77) at time of salvage. The median pre-salvage PSA was 4.56. The biopsy Gleason score of the nodular recurrences was 7 or 8. Median volume of nodular recurrence was 16cc, median number of sources was 30, median D90 for nodule was 155.02 Gy, and median rectum V100 was 0.01. Compared to baseline prior to salvage, patients have reported no additional urinary symptoms or sexual side effects from salvage. Patients have been followed for a median of 28 months post-salvage (range 4-48 months) with a median PSA at last follow up of 1.05. Conclusions: This report presents the first known case series of prostate cancer patients treated with RP who developed local nodular recurrences which were then treated with LDR brachytherapy. For patients who develop a nodular recurrence with no other evidence of distant metastases, LDR brachytherapy offers a novel salvage option. No significant financial relationships to disclose.
CyberKnife for prostate cancer: Is it cost-effective?
Authors: Parthan A. , Pruttivarasin N. , Taylor D. , Davies D. , Yang G. , Pawar V. , Weinstein M. C. 
Published: February 2017

87 Background: The study assessed the cost-effectiveness of CyberKnife (CK) compared to surgery and radiation therapy for the treatment of prostate cancer (PC) from a third-party and societal perspective. Methods: For patients > 65 yrs with localized PC, a Markov model compared treatment with CK, intensity modulated radiation therapy (IMRT), surgery or proton therapy (PT). Following treatment, patients were at risk of long-term toxicity: genitourinary (GU); gastrointestinal (GI); and sexual dysfunction (SD). Long-term toxicity was defined as adverse events >grade 2 on Radiation Therapy Oncology Group scale occurring at least 12 months following treatment. Markov states included all possible combinations of GI, GU, and SD long-term toxicities, no toxicity, and death. During each year patients remained in the same Markov state or died. Costs and utilities were assigned using published sources. Toxicity probabilities were derived using meta-analytical techniques to pool results from multiple studies. It was assumed that long-term disease control would not differ across treatments. The model projected expected lifetime costs and quality adjusted life years (QALYs) for each treatment and incremental cost-effectiveness of CK vs comparators as cost per QALY gained. Costs from societal perspective included lost productivity. Extensive sensitivity analyses were conducted. Results: Surgery was the least expensive treatment option followed by CK. CK patients had higher expected QALYs (8.11) than other treatment options (7.72- 8.06). From a payer perspective, total lifetime costs were $25,904, $22,295, $38,915, and $58,100 for CK, surgery, IMRT and PT, respectively. Incremental cost per QALY gained for CK versus Surgery was $9,200/QALY. Compared to IMRT and PT, CK was less costly and resulted in higher QALYs (dominance). At a threshold of $50,000/QALY, CK was cost effective in 86%, 79%, and 91% of simulations compared to surgery, IMRT, and PT, respectively. From a societal perspective, CK costs $4,200/QALY compared to surgery and remained dominant vs IMRT and PT. Results were most sensitive to costs of surgery and CK. Conclusions: Initial CK costs are higher than surgery, but CK patients have better quality of life. CK patients have lower lifetime costs and higher QALYs than IMRT and PT patients. [Table: see text]
Stereotactic body radiotherapy for treatment of organ-confined prostate cancer: Efficacy and quality of life at 4 years.
Authors: Katz A. J. , Santoro M. 
Published: February 2017

88 Background: The purpose of this study is to assess the efficacy and toxicity of stereotactic body radiotherapy for organ confined prostate cancer patients. Methods: Fifty T1cN0M0 prostate carcinoma patients (42 low- and 8 intermediate-risk) received 5 fractions of 7 Gy SBRT with Cyberknife to a total dose of 35 Gy delivered over 5 consecutive days. Mean patient age was 69.5 years and mean pre-treatment PSA was 5.7 ng/mL. All patients received 1500 mg of amifostine intrarectally prior to each SBRT fraction. Patients were treated to the 83%-87% contour line with 5-mm margins added to the gross tumor volume at all borders except for the rectum where a 3-mm margin was added. During treatment, 4 gold fiducial seeds were continuously tracked. Toxicity was assessed using the Radiation Therapy Oncology Group toxicity scale; biochemical failure was assessed by the Phoenix criteria, and quality of life was assessed with the Expanded Prostate Cancer Index Composite Questionnaire (EPIC). Results: At a median follow-up of 48 months (range, 46-53 months) one biochemical failure has occurred. Three patients died of intercurrent disease. The median PSA at 48 months is 0.10 ng/mL (range, 0.01-3.5 ng/mL). At 42 months, 42 of 47 patients had achieved a PSA of 0.5 ng/mL or less. Toxicity has been minimal with no grade 3+ toxicities. Actuarial 48 month rates for grade 2 urinary and rectal toxicity-free survival were 95.5% and 97.8%, respectively. Mean EPIC bowel and urinary quality of life returned to baseline by 18 months and remain at baseline values at 36 months. Of the 36 patients that were potent prior to treatment 29 (80.5%) maintained potency. Conclusions: At 48 months median follow-up the promising biochemical control, minimal toxicity and the promising potency preservation rates are highly encouraging. [Table: see text]
Utilizing metformin as a radiosensitizing agent in the treatment of prostate cancer.
Authors: Klotz L. , Venier N. , Vandersluis A. , Besla R. , Fleshner N. , Pollak M. N. , Venkateswaran V. , Colquhoun A. J. 
Published: February 2017

89 Background: External beam radiation therapy (EBRT) is a well recognized curative prostate cancer (PCa) treatment modality utilizing ionizing radiation (IR). In addition to mediating DNA damage, IR upregulates several intracellular pro-survival pathways including the insulin- like growth factor (IGR) signaling network. This may contribute to the intrinsic radioresistance exhibited by certain tumors. Diabetic patients with PCa experience poorer outcomes following EBRT than their non-diabetic counterparts. Some attribute this to diabetes-induced chronic hyperinsulinemia with consequent upregulation of pro-survival insulin/IGF signalling. Previous work by our group showed diet-induced hyperinsulinemia to enhance PCa tumor growth in vivo. Metformin, a diabetic treatment, alleviates hyperinsulinemia, and also exhibits anti-neoplastic properties. We postulate that pre-treatment with metformin to correct hyperinsulinemia may protect cells from radiation-mediated pro-survival insulin/IGF signaling. Thus we assessed the radiosensitizing potential of metformin using in vitro and in vivo PCa models. Methods: The effect of IR and/or metformin on colony formation rates was assessed in LNCaP, PC3, DU145 and PC3AR2 PCa cell lines using clonogenic assay. The combination treatment regimen was assessed in vivo using a murine xenograft model. Western blot and cell cycle analyses are ongoing to try and elucidate any mechanisms of interaction between metformin and IR. Results: Monotherapy with IR (1-8Gy) or metformin (0.01-10.0mM) caused significant dose-dependent reduction in colony formation rates (p<0.001). Combination treatment further significantly reduced colony formation rates (p<0.03). Preliminary results from our in vivo study show diminished tumor growth in response to combination treatment (p<0.0001), and are currently subject to ongoing statistical analyses. Conclusions: Our in vitro findings confirm combining metformin with IR significantly reduces PCa cell colony formation rates further than either monotherapy. Recapitulation of these results in vivo would provide justification for translating this work into a phase II clinical trial of metformin as a radiosensitizing agent. No significant financial relationships to disclose.
Predicting intrafraction displacement of the prostate during a five-fraction radiotherapy regimen: Implications for stereotactic body radiotherapy.
Authors: Quon H. C. , Loblaw D. A. , Cheung P. , Cesta A. , Holden L. , Tang C. I. , Pang G. , Morton G. , Mamedov A. , Deabreu A. 
Published: February 2017

90 Background: Accurate characterization of prostate displacement during stereotactic body radiotherapy (RT) may help optimize margins to maximize complication and disease-free survival. Also, if individual patients with large intrafraction displacement can be identified, additional interventions can be undertaken. Methods: Fifty-three men treated on a phase I/II study of extreme hypofractionation were selected for the study. A total dose of 35 Gy in 5 fractions was delivered with intensity modulated radiotherapy (IMRT). Daily image guidance was performed using gold seed fiducials. Position verification was obtained with orthogonal electronic portal images taken immediately before and after each fraction. Prostate shifts were recorded in 3 dimensions. Results: The mean intrafraction prostate displacements were -0.03 ± 0.61 mm (1SD), 0.21 ± 1.50 mm, and -0.86 ± 1.73 mm in the lateral, superior-inferior, and anterior-posterior directions, respectively. The mean intrafraction displacement during the first two fractions is moderately correlated with the displacement in the remaining 3 fractions, with correlation coefficients of 0.63 and 0.47 in the SI and AP directions, respectively. Conclusions: The mean intrafraction prostate displacement during a course of extreme hypofractionated radiotherapy is small. A strategy using the first two fractions to predict future displacements >5mm shows promise and warrants further validation. No significant financial relationships to disclose.
Treating intermediate-risk prostate cancer with hypofractionated external beam radiotherapy alone.
Authors: Dal Pra A. , Faria S. , Cury F. L. , David M. , Duclos M. , Shenouda G. , Souhami L. 
Published: February 2017

93 Background: A wide range of therapeutic alternatives is available for the treatment of intermediate-risk prostate cancer (IRPC). The use of hypofractionated external beam radiotherapy (HypoRT) in this group of patients appears to be an attractive option. Non-randomized institutional results have provided similar outcomes to conventional fractionation. For health-systems such as we have in Canada, where many patients live far, it significantly shortens treatment duration and impacts favorably in health costs. We report our results using HypoRT alone in IRPC. Methods: Between October/2002 and July/2009, 82 men with IRPC (T2b-T2c, or PSA 10–20 ng/dL, or GS=7) were treated with HypoRT, without any androgen deprivation. Ultrasound image guidance was used daily to confirm setup. The dose was 66 Gy in 22 daily fractions of 3 Gy (BED=79.4Gy/44) prescribed at the isocenter. PTV was the prostate (+/− 1cm seminal vesicles) with 7-mm margin in all directions. GI and GU toxicity were prospectively assessed every 4–6 months using the CTCAE v3 scoring system. Biochemical failure was defined as nadir PSA + 2 ng/dL. Results: 60% of patients had Gleason score 7; 43% had stage T2; median initial PSA=9 ng/ml; median age 71 years. With a median follow-up of 43 months (range: 7–89), only three patients (4%) have developed biochemical failure. All three showed metastatic disease few months after biochemical failure. Actuarial biochemical recurrence free survival (bNED) is 95.4%. There was no death related to prostate cancer. Three patients died from other causes without biochemical failure. The 5-year overall survival was 93%. At the last follow up visit, grade ≥ 2 late GI and GU toxicity rates were 2% and 7%, respectively. No grade 4 or 5 has occurred. Conclusions: Men with IRPC treated with 66Gy/22 fractions and without androgen deprivation have experienced excellent 5-year biochemical control rate with acceptable late toxicity. This regimen is very convenient because the duration of the treatment is half of the time used with conventional fractionation. Whether the addition of short-term androgen deprivation would further improve outcome remains unclear. No significant financial relationships to disclose.