bluuebunny/crossref_metadata_2025 huggingface dataset:
The altered expression of Paraoxonase 1 in the gastric carcinoma.
Authors: Kim Sung Soo , Kim Jin Soo
Published: February 2018

94

Background: High doses inadequate removal of reactive oxygen species result in oxidative stress, which may cause severe metabolic malfunctions and damage to biological molecules including DNA An elevated oxidative status has been found in many types of cancer cells and helicobacter infection. Paraoxonase 1 is one of the endogenous free radical scavenging systems in the human and believed to be involved in the protection against oxidative stress. It has been reported that serum levels of Paraoxonase 1 were lower in patients with pancreatic or gastric cancer than in healthy controls. But there was no study about differential Paraoxonase 1 expression in gastric cancer tissue compared to adjacent non-tumor tissue. In this study, we investigated the changes of Paraoxonase 1 expression in the helicobacter pylori infection and gastric cancer. Methods: 109 gastric cancer tissues and 109 adjacent non-tumor tissues were obtained from 109 patients who received gastrectomy for curative resection. Eighteen H. pylori-positive patients who successfully eradicated were involved. Expression of Paraoxonase 1 and Malondialdehyde was assessed by immunohistochemistry using a tissue microarray method. Results: The intensity of immunohistochemical stain on Malondialdehyde and Paraoxonase 1 was significantly elevated in pre-eradication state compared to post-eradication (1.77 vs 1.05, 1.83 vs 1.11, P< 0.05) of helicobacter infection. The intensity of Malondialdehyde was significantly elevated in gastric carcinoma than adjacent non-tumor area (1.22 vs 0.39, P< 0.05). But intensity of Paraoxonase 1 showed no significant difference in both area (0.55 vs 0.68, P> 0.05). Conclusions: Paraoxonase 1 may be one of antioxidant enzyme in H. pylori induced gastritis. In the gastric carcinoma, it’s role may need further study to conclude.
Immunological changes during intraperitoneal growth of colorectal cancer.
Authors: Heo Seung Chul , Kim Jie-Eun , Shin Rumi
Published: February 2018

97

Background: Immunoediting other than PD-1 works in colorectal cancer (CRC), except for some MSI high tumors. Study of immune response to cancers in the primary CRC is difficult due to interference by the colonic microorganisms. If a clinical model reflecting tumor progression, free from microbial antigens and characterizing the microenvironment is developed it will help us understand the immunoediting of CRC. We studied immunologic changes, according to the peritoneal tumor progression, in ascites and peritoneal immune cells of CRC patients. These results will provide clues to the immunoediting of CRC and to immunotherapy of peritoneal carcinomatosis. Methods: Ascites and peritoneal cells were collected from CRCs during surgery or malignant ascites drainage. Forty-two immune molecules and ratios of immune cells were assayed. Patients with intestinal perforation or leukocytosis were excluded to remove interference by the foreign antigens. Patients were grouped according to the peritoneal tumor progression (PC stages) as follows; SE-: without peritoneal exposure of cancer cells (T3 or lower T stage, no tumor cells in peritoneal cavity); SE+: with peritoneal exposure without peritoneal seeding (T4, microscopic tumor cells in peritoneal cavity); l-PC: localized peritoneal seeding; g-PC: generalized peritoneal seeding. Molecular and cellular changes were evaluated according to PC stages. Results: Of the 42, five (IL-10, IL-6, VEGF, CCL20 and TGF-b) increased with the PC stage progression, meanwhile IL-18 decreased. CXCL8 was elevated in only g-PC. However, 14 molecules could not be assayed due to lower level than the references and other 3 could be assayed in only some g-PCs. The other 18 were not different among PC stages. Especially, IL-10 is a prognostic factor of peritoneal recurrence in SE+. IL-10 and IL-6 are highly correlated. The ratio of CD56+ cells, but not the others, increased according to PC stages. Conclusions: Intraperitoneal CRC growth accompanied IL-10, IL-6, VEGF, CCL20, TGF-b and NK cell increase, meanwhile IL-18 decrease. IL-10 is a prognostic factor of peritoneal recurrence. Identification of secreting and targeting cells of each molecules as well as immune network will provide the clues to immunoediting of CRC.
Phase I trial of safety of combining BCG with pembrolizumab in patients with high grade superficial bladder cancer unresponsive to previous intravesical therapy.
Authors: Alanee Shaheen Riadh , Robinson Kathy , Sana Sherjeel
Published: February 2018

TPS111

Background: Bacille Calmette-Guerin (BCG) is the most effective agent in the treatment of high grade superficial bladder cancer (HGSBC); however, not all patients respond to BCG, and recurrent disease is associated with a poor prognosis. The blockade of immune checkpoints of the pathway involving programmed death 1 (PD1) has been shown recently to be effective in cancer therapy. We started the first trial in the United States to combine an anti-PD1 drug (pembrolizumab) with BCG therapy in patients with HGSBC. Methods: The primary objective of the study was to determine the safety of administering a 200 mg fixed dose of pembrolizumab in conjunction with intravesical BCG treatment in HGSBC patients who have failed two courses of induction therapy or one course of BCG induction therapy followed by maintenance therapy. Patients included had to have pathologically documented HGSBC (Ta, T1) at time of restaging, or have pathologically documented high grade CIS of the bladder at time of initial resection for recurrent/persistent bladder cancer. Subjects were treated with six cycles (21 day cycle) of pembrolizumab treatment combined with six consecutive weeks of concurrent BCG installation beginning with cycle 3 of pembrolizumab. The first three subjects were to be treated at a dose of 100 mg pembrolizumab to ensure safety for the combination. If no safety issues were to happen, dosing was to be escalated to 200 mg every three weeks. Our secondary objective was to determine the 19 week and the three, twelve, and twenty-four month post-treatment completion complete response rate. The first patient received cycle 1 of pembrolizumab treatment in July of 2015. As of the date of writing this letter, five patients have completed treatment on this trial. The trial is soon to open a second site at Henry Ford Health System in addition to Southern Illinois University with the goal of full enrollment to be achieved in the next 6 months. Clinical trial information: NCT02324582.
Oral cavity squamous cell carcinoma and Waldeyer ring squamous cell carcinoma PDL-1 expression: A large, retrospective, single institution site series on head and neck squamous cell carcinoma, looking at the relationship with morphology, human papilloma virus and p16.
Authors: Yeoh Chit Cheng , Akaev Iolia , Glaysher Sharon , Chopra Mridula , Krol Anzhela , Rahimi Siavash
Published: February 2018

TPS119

Background: The most frequent type of epithelial malignancy in oral cavity and Waldeyer's ring (WR) is squamous cell carcinoma (SCC). Patients with Head and Neck SCC (HNSCC) show reduced levels of CD3+, CD4+, and CD8+ T cells compare to healthy controls. SCCs with a higher number of intra-tumoural CD4+ and CD8+ lymphocytes are associated with better prognosis. Programmed death receptor ligand (PD-L1 ) is present on the surface of neoplastic cells in SCC. T cells harbour inhibitory receptors (the so-called immune checkpoints) such as PD-1. Activation of this immune checkpoints results in T cell deactivation. The PD-1/PDL-1 interaction provokes an immunosuppressive effect which allows the tumour to evade immune destruction. However, WR SCCs present some diversities comparing to oral cavity SCC: younger age, frequent neck LN metastasis, often cystic, distinct morphology: often undifferentiated and solid (nonkeratinizing basal cell morphology), better prognosis, often HPV+, often p16+, an increased number of CD56+ cytotoxic NK. Methods: We have a series of 90 cases of epithelial malignancy in oral cavity and Waldeyer's ring (WR)Squamous cell Carcinoma, registered for Ethics IRAS number for Translational study with Immunohistochemistry; Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR); Fluorescence in Situ Hybridisation (FISH); Next Generation Sequencing; Digital Imaging scanning and visualising microscopy. The Study will show the relationship of PDL-1 expression with morphology, Human Papilloma Virus (HPV) infection and p16 expression, answering if the oral cavity SCC and Waldeyer's Ring SCC express PD-L1 in the same way.
Ten year final results of the TROG 03.04 (RADAR) randomised phase 3 trial evaluating duration of androgen suppression ± zoledronate for locally advanced prostate cancer.
Authors: Joseph David John , Lamb David S , Denham James William , Oldmeadow Christopher , Attia John , Steigler Allison
Published: February 2018

1

Background: We investigated whether 18 months of androgen suppression (AS) plus radiotherapy (RT) ± 18 months of zoledronate (Z) is more effective than 6 months of neoadjuvant AS plus RT ± Z. Methods: Eligible men with T2a-4, N0, M0 prostatic adenocarcinomas with PSA ≥10 and Gleason score (GS) ≥7 in T2a cases were randomly allocated in a 2x2 factorial trial design to 6 months neo-adjuvant AS using leuprolide (22.5mg i.m. 3 monthly) and radiation (control arm) or followed by treatment factor 1- 12 months AS (22.5mg i.m. 3 monthly), or accompanied by the second treatment factor 2- 18 months Z (4mg i.v. 3 monthly) starting at randomisation, or by both treatment factors. Patients were stratified by centre, baseline PSA, tumour stage, GS, and use of a brachytherapy boost. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included time to PSA, local, distant, bone and soft tissue progressions (PSA, LP, DP, BP and STP) and time to secondary therapeutic intervention and all-cause mortality (STI and ACM). Endpoints were analysed by intention to treat using competing risks methodology. ACM was analysed using Cox regression. Results: Between October 2003 and August 2007 1071 men were randomised with median age 68.7 years. Median follow-up was 10.4 years (IQR 7.9-11.7). No significant interaction was observed between AS and Z. Significant reductions were observed favouring 12 months AS for the primary endpoint: PCSM sHR 0.70 (0.50-0.97), p = 0.035; and for the secondary endpoints: BP sHR 0.61 (0.45-0.83), p = 0.001; DP sHR 0.71 (0.56-0.90), p = 0.004; PSA sHR 0.65 (0.53-0.78), p < 0.001; LP sHR 0.60 (0.39-0.92), p = 0.021; and STI sHR 0.66 (0.53-0.81), p < 0.0001. There were also non-significant reductions favouring 12 months AS in STP (sHR 0.85 [0.62-1.16], p = 0.30) and ACM (HR 0.84 [0.69-1.03], p = 0.10). The addition of 18 months Z did not influence any outcome significantly. Conclusions: 18 months AS+RT is an effective option for locally advanced prostate cancer but the use of 18 months Z is not beneficial. Clinical trial information: NCT00193856.
A phase II study of degarelix prior to radiation on prostatic tissue androgens.
Authors: Montgomery Robert B. , Russell Kenneth J. , Liao Jay Justin , Ellis William J , Cheng Heather H. , Yu Evan Y. , Mostaghel Elahe A.
Published: February 2018

103

Background: Optimizing androgen suppression may provide better treatment outcomes for localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation (ADT) with definitive radiotherapy in men with locally advanced or high-grade disease. LHRH agonist (LHRHa) is most commonly used. The LHRH antagonist degarelix may provide more robust androgen suppression. The impact on tissue androgens following use of degarelix prior to radiation has not been reported. We examined the impact on androgens in serum and tissue after 12 weeks of degarelix in this phase II study. Methods: A prospective, phase II study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent degarelix with radiation. Prostate biopsies were obtained at the time of fiducial placement before radiotherapy. Serum and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry. Needle biopsies from a separate analysis of untreated men or those receiving LHRHa prior to prostatectomy were used as tissue androgen level controls. Results: 16 men with intermediate (4) and high-risk (12) PCa received study therapy. 14 men completed degarelix and planned radiation to 77.4-81 Gy. Serum and tissue androgens after 12 weeks of therapy are compared to untreated control and LHRHa treated patients (12 weeks). Serum levels of dihydrotestosterone (DHT) and testosterone were similarly suppressed by LHRHa or degarelix compared to untreated controls, without statistically significant differences. Degarelix provided statistically greater reduction in androsterone than LHRHa. Conclusions: In this phase II study degarelix and LHRHa achieved similar serum and tissue androgen levels at 12 weeks; however, there was a greater suppression of tissue androsterone with degarelix. The clinical significance of this difference remains uncertain. Clinical trial information: NCT01731912. [Table: see text]
Improving risk-stratification of localized prostate cancer in a prospective active surveillance cohort.
Authors: Gregg Justin , Reichard Chad A. , Wang Xuemei , Chapin Brian Francis , Pisters Louis L. , Pettaway Curtis Alvin , Ward John Francis , Achim Mary F. , Choi Seungtaek , Kuban Deborah A. , Davis John W. , Kim Jeri
Published: February 2018

104

Background: Prospective active surveillance (AS) studies in men with low- and intermediate-risk prostate cancer (PCa) have demonstrated feasibility, but no consensus supports an optimal monitoring scheme. To expand our findings on AS disease reclassification, we examined predictors of disease reclassification in a prospective single-institution AS study. Methods: Men with localized PCa diagnosed within 6 months (mos) of AS enrollment were stratified into four groups: group 1 (Gr 1) was defined by a Gleason score (GS) ≤6 (3+3), one positive (pos) core ( < 3 mm), and a prostate-specific antigen (PSA) level < 4 ng/mL (adjusted by prostate size); Gr IIa by GS 6, one pos core, and either tumor length ≥3 mm or PSA ≥4 ng/mL; Gr IIb by GS6, > one pos core, and any PSA level or tumor length; Gr IIc by GS7, > one pos core or any PSA. Monitoring included PSA and digital rectal exam every 6 mo. Biopsy (BX) was repeated at 1 year and then on a predetermined BX scheme. Patients with reclassified disease (upgrading, increase in pos cores and/or tumor length) were offered treatment. Cox proportional hazards modeling was used to determine the association of baseline clinicopathologic parameters with time to reclassification. Results: Between 2006 and 2015, 803 patients met criteria for inclusion: Gr I, 242; Gr IIa, 67; Gr IIb, 376; Gr IIc, 118. Median age was 64 years (range, 36–83), 662 (82.4%) were white, 703 (87.5%) had cT1c disease, 687 (85.6%) had GS 6, and median PSA level was 4.2 ng/mL (range 0.2–34). At a median follow-up of 2.9 years, 249 (31.0%) men had disease reclassification and 258 (32.1%) left AS to pursue curative treatment. Overall, 82% of reclassifications occurred within 3 years of study enrollment. Stratification to group IIb/IIc was significantly associated with time to reclassification compared to Gr I/IIa (HR 2.13, 95 CI 1.63-2.80, p < 0.001) while CAPRA score did not show a significant difference (p = 0.27). Conclusions: Grouping patients on characteristics including tumor length and pos core number may improve risk stratification in localized PCa. Risk-based surveillance protocols merit further evaluation. Clinical trial information: NCT00490763.
Phase II trial of 6 months ADT/abiraterone acetate plus prednisone (AAP) and definitive radiotherapy (AbiRT) for men with intermediate to high risk localized prostate cancer.
Authors: Koontz Bridget F. , Hoffman Karen E. , Healy Patrick , George Daniel J. , Harrison Michael Roger , Zhang Tian , Lee W. Robert , Berry William R. , Pugh Thomas J , Corn Paul Gettys , Bratt LuEllen , Shobe Kellie , Thornburg Blair , Allen Donna M. , Brummer Katie , Tojong Beth , Hobbs Bridget , Halabi Susan , Armstrong Andrew J.
Published: February 2018

11

Background: Combined external beam radiotherapy (RT) and androgen deprivation therapy (ADT) improves survival over RT alone for high risk prostate cancer (PC). Long-term ADT use, currently recommended for high risk PC, also increases toxicity. Recent data suggests synergistic efficacy with the addition of abiraterone acetate plus prednisone (AAP) to RT/ADT. Potent androgen blockade may provide biochemical control with short-term ADT course in men with aggressive but localized PC. Methods: This was a two center prospective phase 2 single arm clinical trial within the Department of Defense PCCTC (NCT01717053). Eligibility included 2+ intermediate or 1 high NCCN risk factors and no metastatic disease. Men received 6 months of ADT concurrently with 1000mg AA/5mg P daily and 78 Gy RT to prostate/SV. Primary endpoint was PSA < 0.1 ng/ml at 1 year. Secondary objectives included BPFS, PSA nadir, testosterone recovery, toxicity, and patient-reported QOL. Results: We enrolled 37 men (82% white, 18% black) with intermediate to high risk localized PC; 33 completed course of treatment (4 patients halted early for personal preference (N = 2), planned prostatectomy, or renal artery stenosis). Median age was 66 years; 46% Gleason 8-10, 40% Gleason 4+3 = 7, 62% T1c. Median follow-up is 23 months. Regimen was well tolerated with 12 (32%) G3 toxicities (10 hypertension, 2 hyperglycemia, 1 hypokalemia); no G4-5 or unexpected toxicities were observed. At 12 months from enrollment, PSA remained at undetectable levels in 52% of men. Testosterone recovery to normal lab value occurred in 12 (62%) at 12 months. In those patients, 20 (95%) and 21 (100%) remained with PSA under 0.5 and 1.0 ng/ml, respectively. No patient has failed by Phoenix definition to date. 1 year EPIC QOL had median summary scores above 90 for incontinence, urinary, bowel, hormonal, and satisfaction. Sexual summary score fell from median of 46 at baseline to 26 at 1 year. Conclusions: In men with high risk intermediate or limited high risk PC, utilizing short-term ADT/AAP with definitive RT shows 1) high rate of testosterone recovery and good quality of life and 2) excellent PSA control at 1 and 2 years. Clinical trial information: NCT01717053.
National trends in the management of patients with positive surgical margins at the time of radical prostatectomy.
Authors: Ghabili Kamyar , Nguyen Kevin , Hsiang Walter , Syed Jamil , Suarez-Sarmiento Alfredo , Shuch Brian M. , Park Henry Soo-Min , Yu James B. , Leapman Michael
Published: February 2018

111

Background: The optimal management approach for patients with positive surgical margins (PSM) at radical prostatectomy (RP) has not been definitively assessed. To better understand contemporary patterns of care, we sought to examine time trends and determinants of adjuvant therapy in a large national sample of men with prostate cancer (PCa) treated with RP. Methods: We queried the National Cancer Database (NCDB) to identify men with clinically-localized PCa diagnosed from 2010 to 2014 who had PSM at RP performed as initial primary definitive treatment. We used descriptive statistics to examine subsequent management strategies, assessed as no adjuvant therapy as part of the initial planned course of management, receipt of adjuvant radiation therapy (RT), and receipt of adjuvant RT in combination with androgen deprivation therapy (ADT). Binary logistic regression models were constructed to identify patient, tumor, and facility features associated with receipt of adjuvant therapy. Results: During the study period, we identified 44,523 patients with PSM. Of those, 5,179 (11.6%) men received any adjuvant RT (+/- ADT), while only 1,380 (3%) received adjuvant RT with ADT. Use of adjuvant RT did not change over the study period ( p= 0.61). On multivariable analysis men of uninsured status (p = 0.003), Medicaid insurance (p = 0.001), and patients treated in non-academic facilities (p < 0.001) were more likely to receive adjuvant RT. In addition, use of adjuvant RT was associated with higher pre-treatment PSA (p < 0.001), pathologic stage (p < 0.001) and Gleason grade group (p < 0.001), decreasing distance from the treatment center (p < 0.001), and shorter duration between diagnosis and RP (p < 0.001). Receipt of adjuvant ADT with RT was associated with clinical and pathologic features; however, not with sociodemographic factors. Conclusions: The majority of patients experiencing PSM at RP did not receive adjuvant RT, and rates of adjuvant therapy have remained stable over time. In addition to adverse clinical and pathologic features, sociodemographic and facility factors were significantly associated with receipt of adjuvant RT; however, the addition of ADT appears largely driven by disease characteristics.
Are all biopsies created equal? comparison of extended sextant prostate biopsies performed with and without MRI-TRUS fusion biopsy system.
Authors: Hale Graham R. , Bloom Jonathan , Sabarwal Vikram , Gold Samuel , Rayn Kareem , Wood Brad J. , Turkbey Baris , Pinto Peter A. , Hwang Tyler
Published: February 2018

117

Background: Extended sextant systematic prostate biopsies have the inherent risk of under-sampling prostate cancer. Fusion guided multiparametric magnetic resonance imaging (mpMRI) biopsies have been employed to better represent the disease and guide treatment. We sought to determine if due to heightened suspicion of cancer and/or visualization of mpMRI there were any discrepancies between systematic biopsies done with a Fusion System as compared to those done without (TRUS alone). Methods: From a prospectively collected database, we performed a review collecting age, race, clinical stage, PSA, and time until repeat systematic biopsy as part of fusion guided biopsy (IB). We also collected pathology results reported as Gleason Score (GS), for both the patients’ OB and our IB. Patients were stratified into groups based on time between OB and IB/fusion biopsy ( < 6 months, < 1 year and < 2 years). Results: 69 patients with a previous OB underwent combined fusion and IB within our designated time intervals. Cancer detection rates between the OB and IB results were similar at 6 months, 1 year and 2 years (80 vs 90%, 87.5 vs 87.5% and 65 vs 69%). Detection rates of GS ≥ 3+4 were higher with IB within 12 months compared with IB from 12-24 months (72.7 vs 40.9%, p = 0.03 OR 3.85 (1.09-13.66). Of the patients who were upgraded (n = 24), 54.2% (n = 13) went from benign pathology to a diagnosis of prostate adenocarcinoma. Of all OB GS 3+3 (n = 31), 29% were restaged to higher risk disease on IB. Rates of IB upgrading were similar within 6 months, 1 year and 2 year, 40%, 33.33% and 31.91%). Patients who were upgraded on IB compared to those who were not upgraded were of similar age (67.0 ± 6.53 vs 66.50 ± 6.47), race (17.4% African-American vs 13%), PSA (7.60 ± 5.61 vs 7.50 ± 4.39) and prostate volume on MRI (51.30 ± 26.87 vs 59.26 ± 38.52). Conclusions: A systematic biopsy at our referral center during a mpMRI fusion biopsy was over 3.5 times more likely to detect GS ≥ 3+4 when done within 1 year of the outside biopsy. There continued to be a risk, 34.7% overall, of disease upgrading in all time periods. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH
The association between physician trust and prostate specific antigen screening: Implications for shared decision making.
Authors: Klaassen Zachary William Abraham , Wallis Christopher J.D. , Goldberg Hanan , Chandrasekar Thenappan , Fleshner Neil Eric , Finelli Antonio , Kulkarni Girish S. , Satkunasivam Raj
Published: February 2018

13

Background: Most cancer organizations recommend shared decision making for PSA screening, a process relying on a trusting relationship between patient and physician. The objective of this study was to assess the degree to which an individual’s trust in cancer information from their physician compared to internet-based information impacts the likelihood of receiving PSA-screening. Methods: This was a cross-sectional study (2011-2014) of the Health Information National Trends Survey (HINTS), a survey of people living in the US. The primary exposure was degree of trust in cancer information from participant’s physician (CIP). The secondary exposure was degree of trust in cancer information from the internet (CII). The primary outcome was patient-reported receipt of PSA-screening. The Cochran-Armitage test was used to identify significant trends in the primary outcome, across levels of trust. A multivariable logistic regression model assessed the association between CIP and CII with PSA-screening, adjusted for a priori covariates. Results: Among 5069 eligible respondents, 3,606 (71.1%) reported trusting CIP ‘a lot’, 1,186 (23.4%) ‘some’, 219 (4.3%) ‘a little’, and 58 (1.1%) ‘not at all’. 2,655 (52.4%) men received PSA-screening. The degree of trust in CIP was strongly associated with the likelihood of receiving PSA-screening: among men who reported ‘a lot’ of trust, 54.9% underwent screening, 48.6% ‘some’ trust, 38.4% ‘a little’ trust, and 27.6% among men ‘not at all’ trusting their physician (trend p < 0.0001). The degree to which men trusted CII was also associated with having received PSA-screening (p = 0.005), albeit with an insignificant trend (p = 0.07). After multivariable adjustment, these significant results persisted for degree of CIP trust (vs ‘a lot’: ‘some’ OR 0.80, 95%CI 0.66-0.97; ‘a little’ OR 0.61, 95%CI 0.41-0.90; ‘not at all’ OR 0.33, 95%CI 0.15-0.73), but not for trust in CII. Conclusions: The level of trust an individual has in their physician is strongly associated with undergoing PSA-screening. As rationale implementation of PSA screening requires shared decision-making, the level of physician trust has implications for dissemination of PSA-screening guidelines.
How many cores are needed to detect clinically significant prostate cancer on targeted MRI-ultrasound fusion biopsy?
Authors: Lu Amanda , Ghabili Kamyar , Nguyen Kevin , Leapman Michael , Sprenkle Preston
Published: February 2018

134

Background: The optimal number of MRI-US fusion biopsy cores to adequately sample regions of interest (ROI) remains unknown. To better understand the optimal approach to lesion targeting, we aimed to examine the cancer detection rate based on sequential number of cores obtained. Methods: Of 744 patients undergoing MRI-US fusion biopsy between 2012 and 2016 at our institution, we identified 628 men with targets on multi-parametric MRI (mpMRI) who underwent targeted and systematic fusion biopsy using the Artemis platform for clinical suspicion (n=465) or known history of PCa (n=163). mpMRI studies were reviewed by genitourinary radiologists using a 3-tiered Likert scale and PI-RADS classification schema. Biopsy was performed by two urologists performing a high volume of fusion biopsies (PS and RD). Cores were taken sequentially from each ROI with an even distribution. The primary outcome was the proportion of high-grade (Gleason ≥3+4) cancers missed on a 2-core lesion biopsy. Results: We biopsied 1,233 ROI with a median of 5 cores (IQR 3-5) from each ROI. A total of 581 ROI (47%) were positive for any Gleason grade PCa, in 380 (61%) patients. On a per-lesion basis, 84% of any Gleason score cancers were detected with a two-core biopsy and 77% of Gleason ≥3+4 tumors. Cancer detection rates improved with increasing number of cores (Table 1). For any Gleason grade PCa, additional cores beyond 5 cores had no significance. For G≥3+4 cancer, there was no significance with additional sampling from 3 to 4 cores, but improved detection from 3 to 5 cores (P<0.05). For PI-RADs 4 and 5 lesions, additional sampling up to 4 cores significantly improves G≥3+4 detection, while for PI-RADs 1-3 lesions sampling up to 2 cores improves detection. Conclusions: On a per-lesion basis, sampling two cores of mpMRI-evident lesions at the time of fusion biopsy misses nearly one-quarter of clinically significant PCa that would be detected on additional sampling. [Table: see text]
Normal Tissue Complication Probability (NTCP) model for erectile dysfunction (ED) following external beam radiotherapy (RT) for prostate cancer.
Authors: Murray Julia , Griffin Clare , Hall Emma , Dean Jamie , Syndikus Isabel , Staffurth John , Mayles Helen , Gulliford Sarah , Dearnaley David P.
Published: February 2018

135

Background: ED remains a common toxicity of prostate RT despite technological advances. Penile bulb (PB) dose has been proposed as a predictor of ED post RT. The main objective of this study was to develop NTCP models for ED. Methods: 162 men treated within the CHHiP IGRT substudy (CRUK/06/16) had baseline clinical data, PB dosimetric data & evaluation of ED using EPIC-26 at least 3 years post RT. Planning CT and reference dose distributions were imported into analysis software (VODCA, MSS GmbH) and PB retrospectively contoured by one clinician. The defined endpoint (severe ED) was a standardised average value of 0-33 for EPIC-26 sexual domain. Predictive models of ED were generated using PB dose in EQD2 (α/β ratio = 3Gy) & clinical data (age, diabetes, hypertension, NCCN risk group, baseline PSA, hormone therapy, IGRT, margin size, PB volume). Multivariate logistic regression method using resampling methods was applied to select model order and parameters. Models were fitted using logistic regression of the form Probability = eA(x)/1+eA(x), where A(x) = constant + sum of (variables * associated regression coefficients). Model performance was evaluated through area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow (HL) goodness-of-fit test. Results: 101/162 (62%) men had severe ED with statistically significant difference in PB max and mean dose between those patients with or without severe ED (max: 61.8Gy vs 43Gy & mean: 27.4Gy vs 14Gy respectively; p = 0.001). In the univariate analyses, age, diabetes, risk group, PB mean and max doses were significantly associated with EPIC calculated severe ED. The optimal NTCP model (AUC 0.78; CI 0.71-0.86: p for HL = 0.75) for EPIC calculated severe ED included age, PB mean dose and diabetes where A(x) = -10.13+(0.14*age)+(0.03*PB mean dose)+(2.88 if diabetic). A comparable model using clinician completed outcomes will be reported. Conclusions: This study provides the first known clinical prediction model for ED including PB dose, with good model performance. The determined predictors for the NTCP model of severe ED in this cohort were PB mean dose, age & diabetes. External validation of this model is desirable. Clinical trial information: 97182923.
What is the accuracy of multi-parametric magnetic resonance imaging in predicting adverse pathology in patients undergoing radical prostatectomy?
Authors: Rai Samarpit , Dervishi Adnan , O'Bryan Brittany Ewing , FitzGibbon Thomas Michael , Knoll Paul , Nguyen Kristy Doan , Ankem Murali , Messer Jamie Christopher
Published: February 2018

139

Background: Few studies have examined the accuracy of preoperative multi-parametric magnetic resonance imaging (MP-MRI) in predicting adverse pathological features in patients undergoing radical prostatectomy (RP) for localized prostate cancer (PCa). Methods: We retrospectively analyzed the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of preoperative MP-MRI for adverse pathologic features [extracapsular extension (ECE), seminal vesicle invasion (SVI), lymph node involvement (LNI) and high Gleason score) on postoperative pathologic staging after RP in 30 patients with localized PCa . Results: The median age and preoperative PSA were 62.5 years and 8.5 ng/mL, respectively.17 patients had ECE, 5 had SVI, 5 had LNI, and 15 had high risk Gleason score (4+3, tertiary pattern 5, 4+4 or higher). The sensitivity, specificity, PPV and NPV of MP-MRI for ECE was 64.71% (95%CI 38.33 - 65.79), 92.31% (95% CI 63.97 - 99.81), 91.67% (95% CI 61.52 - 99.79), and 66.67% (95% CI 40.89 - 86.96) respectively. For the detection of SVI on MP-MRI, the sensitivity, specificity, PPV, and NPV were 60% (95% CI 14.66 - 94.73), 96% (95% CI 76.95 - 99.90), 75% (95% CI 19.41 - 99.37), and 92.31% (95% CI 74.87 - 99.05) respectively. For the detection of LNI, the sensitivity of MP-MRI was 100% (95% CI 47.82 - 100), specificity was 96% (95% CI 79.65 - 99.90), PPV was 83.33% (95% CI 35.88 - 99.58), NPV was 100% (95% CI 85.75 - 100). For detection of of high risk Gleason score the sensitivity of MP-MRI was 94.44% (95% CI 72.71 - 99.86), specificity was 66.67% (95% CI 34.89 - 90.08), PPV was 80.95% (95% CI 58.09 - 94.55), and NPV was 88.89% (95% CI 51.75 - 99.72). Conclusions: MP-MRI has a reasonable sensitivity, specificity, and NPV for the preoperative detection of adverse pathologic features at prostatectomy. This could provide assistance in the selection of patients appropriate for Active Surveillance as well as in the preoperative counseling regarding multimodality treatment for PCa.
Impact of late Medicaid expansion on prostate cancer screening.
Authors: Pucheril Daniel , Zlatev Dimitar V. , Mossanen Matthew , Cole Alexander P , Ingham Matthew D. , Chang Steven Lee , Kibel Adam S. , Trinh Quoc-Dien
Published: February 2018

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Background: A key provision of the Affordable Care Act (ACA) was the expansion of Medicaid to childless adults living < 138% of the federal poverty level (FPL). Aside from a few early expansion states, the majority of states adopting the provision expanded coverage in January 2014, and are categorized as late expansion states (LES). Non-expansion states (NES) opposed expansion and did not adopt these broader provisions. Our objective was to determine the effects of this policy change on prostate cancer screening (PSAS) trends in LES and NES. Methods: The 2014 and 2016 Behavioral Risk Factor Surveillance System surveys reflect 2013 and 2015 health behaviors, and were queried for men 40-64, without history of prostate cancer, with a household income < 138% FPL, and residing in NES or LES. Descriptive statistics, stratified by expansion status and year, were generated for covariates. The Chi-Square test was used to compare proportions between years within state categories. Difference-in-differences (DID) analyses were employed to compare trends in men with health insurance, a personal physician, and undergoing PSAS. Within a multivariable logistic regression model, the interaction term year*state expansion status was used to determine the significance of DID estimates. Results: A weighted 8.8 million (n = 14,979) men met inclusion criteria. PSAS significantly declined from 2014 to 2016 in both NES (22.6% to 16.4%, p = 0.0006) and LES (20.5% to 15.8%, p = 0.003). In LES, the proportion of men with health insurance significantly increased from 2014 to 2016 (75.5% to 82.7%, p = 0.0002), however the proportion of insured men in NES was constant. Additionally, the proportion of respondents with a personal physician was unchanged from 2014 to 2016 in both NES and LES. DID analysis determined a significant difference in health insurance trends between 2014 and 2016 for LES compared to NES (+6.9%, p = 0.008). DID estimates were not significant for comparisons of trends for PSAS or access to a personal physician. Conclusions: The ACA’s Medicaid expansion provision has led to significant gains in insurance coverage for eligible persons in LES compared to NES, however, these gains have not translated into significantly different rates of access to a personal physician or PSAS.
Decipher test’s impact on the postoperative management of prostate cancer.
Authors: Calio Brian P. , Murphy Matt , Calvaresi Anne , Mark James Ryan , Mann Mark , Den Robert Benjamin , Gomella Leonard G. , Trabulsi Edouard John , Lallas Costas D.
Published: February 2018

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Background: The Decipher Prostate Cancer Test provides risk stratification for prostate cancer aggressiveness and predicts the probability of metastasis after surgery. We aim to determine the impact on clinical decision-making Decipher risk designation has had at our institution since its implementation. Methods: A prospectively maintained single institution database was analyzed for patients who underwent prostate biopsy and prostatectomy between 2006-2017. Patients with pathologic T3 cancer, Gleason ≥3+4, or positive surgical margins were considered for the study. In cohort 1, patients’ Decipher scores were available prior to postoperative decision-making, in cohort 2 patients’ scores were not available. Postoperative management was then compared between cohorts to determine if presence of Decipher score influenced the rate of adjuvant and salvage radiation administered. The EMR was queried for the words “adjuvant”, “RT”, “salvage”, “SRT”, to record rates of radiation given to each patient. Chi Square and Mann Whitney test was used to compare rates between cohorts and Decipher risk categories. Results: 454 patients were included in the study with median (IQR) age of 62.0 (7.0) years. Mean time of follow-up was 2.0 years and 8.2 years in cohorts 1 and 2, respectively. In the cohort that received Decipher scores, rate of adjuvant radiation administered was significantly higher than in patients who did not receive a Decipher score (27.0% vs. 6.8%, p<0.001), and higher Decipher risk was associated with higher rate of adjuvant administration (9% vs 27.8% vs 35.4% for low, average and high risk, respectively; p<0.001). Rate of salvage radiation given was not significantly different between the cohorts (5.2% vs 4.0%; p=0.228). Conclusions: The Decipher Prostate Cancer Test provides valuable data regarding risk stratification of disease. As demonstrated here, the availability of Decipher scores has lead to a demonstrable effect in the postoperative management of prostate cancer.
Changing trends in prostate brachytherapy practice for clinically localized prostate cancer: Results of a survey in UK and Ireland.
Authors: Corey Gemma , Mohamed Yoosuf Ahamed Badusha , Byrne Monica M. , Workman Geraldine , Mitchell Darren M. , Jain Suneil
Published: February 2018

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Background: High Dose Rate (HDR) and Low Dose Rate ( LDR) prostate brachytherapy (PBT) with or without external beam radiotherapy provide excellent biochemical outcomes with practice adapting to ongoing research and technological advances. We wished to document current PBT practice in the UK and Ireland (UK & I) and compare with previous published audit results. Methods: A link to an online survey was communicated to centres attending the UK & I PBT conference in 2017 (n = 25). Sixty-three questions were grouped into six themed sections which included current experience, staffing, implant numbers (last 3 years), LDR pre / post implant dosimetry and HDR technique. Descriptive analysis was performed. Results: 18 of 25 centres responded (11 LDR only, 6 HDR & LDR, 1 HDR only) with 13 and 3 centres having > 10yrs experience with LDR and HDR respectively. 13 centres have two or more oncologists and 15 centres have two or more medical physics experts (MPE). 61% of lead clinicians performed > 25 implants with 22% performing > 50 in the year 2016. In the preceding 3 years, 44% of centres reported the number of LDR monotherapy cases as stable while 44% noted a reduction in numbers. Similarly 40% of centres reported LDR boost cases as stable, 40% as reduced and 20% with increased cases. The number of centres using HDR treatment as boost, monotherapy and salvage therapy has increased, with increased cases in the year 2016 as compared to 2014. Comparison with the UK 2012 audit showed that post implant LDR dosimetry is more consistently performed and the majority of cases were achieving the 3 defined quality standards of D90, V100 and CT:USS volume ratio. Average post implant D90 was > 145Gy in 63% of centres in 2014 and 2015 compared to 70% in 2016. 50% of centres reported average D90’s of > 155Gy in all three years surveyed. Conclusions: This survey offers a review of PBT practice across UK and I with an apparent fall in LDR monotherapy and boost cases but increase in HDR numbers noted. Surveyed centres report dosimetrically good quality implants. Current research supports PBT as a definitive primary treatment which should be discussed with eligible men at diagnosis.
The FALCON trial: Impact of 18F-fluciclovine PET/CT on clinical management choices for men with biochemically recurrent prostate cancer.
Authors: Teoh Eugene Jueren , Bottomley David M. , Scarsbrook Andrew , Payne Heather , Afaq Asim , Bomanji Jamshed , Van As Nick , Chua Sue , Hoskin Peter , Chambers Anthony , Cook Gary J. , Warbey Victoria S. , Chau Albert , Ward Penelope , Miller Matthew P. , Stevens Daniel J. , Wilson Lynn , Gleeson Fergus V.
Published: February 2018

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Background: Detection of the extent of local recurrence and of metastases in biochemical recurrence (BCR) of prostate cancer facilitates selection of appropriate treatment. The FALCON trial (NCT02578940) assessed the impact of 18F-fluciclovine PET/CT on the clinical management of men with BCR of prostate cancer following initial radical therapy. Methods: Men being considered for curative-intent salvage therapy following first BCR were recruited at 6 UK sites. Management plans were documented prior to and following 18F-fluciclovine PET/CT imaging. Post-scan changes to treatment modality such as salvage radiotherapy [RT] to systemic therapy were classed as ‘major’, while changes within a modality (e.g. modified RT fields) were classed as ‘other’. A pre-planned interim analysis of the first 85 patients was conducted; recruitment was to be stopped for efficacy if the number of treatment changes was > 45 (52.9%; 97.5% CI: 40.3–62.3%), or for futility if ≤ 8 (9.4%, 97.5% CI: 3.6–18.9%). Results: The 85 enrolled patients were a mean 4.8 y post-initial diagnosis, with a median age of 67 y and median PSA of 0.63ng/mL. Twelve (14.1%) had a Gleason score ≤ 6, 60 (70.6%) had a score of 7 and 13 (15.3%) had a score ≥ 8. Most (56; 65.9%) had previously undergone radical prostatectomy (RP), with 27 having received RT (± other therapy). The majority of those imaged (52; 61.2%) had a change in management (CIM) post-scan (Table). Recruitment was subsequently stopped as the pre-specified condition defining overwhelming efficacy was met. Conclusions: This prospective trial shows 18F-fluciclovine PET/CT has substantial impact on clinical decisions for men with a first BCR of prostate cancer after curative-intent primary therapy. Clinical trial information: NCT02578940. [Table: see text]
Can free PSA be used as a biomarker in biochemical recurrence after surgery to predict castrate resistant prostate cancer?
Authors: Goldberg Hanan , Hoffman Ally , Woon Teck Sing , Klaassen Zachary William Abraham , Chandrasekar Thenappan , Cheung Douglas , Berlin Alejandro , Sayyid Rashid , Fleshner Neil Eric
Published: February 2018

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Background: PSA produced from prostate cancer (PC) cells escapes proteolytic processing, resulting in a more complexed PSA and a lower %fPSA. Higher %fpsa correlates with lower PC risk. However, the role of fPSA in biochemical recurrence (BCR) after radical prostatectomy (RP) is unknown. Methods: All patients who had BCR after RP and at least one fPSA test, were included. Patients were stratified according to the %fPSA cut-off of 0.15. Multivariable logistic regression analysis was performed to predict covariates associated with a higher %fPSA. Results: A total of 81 men with BCR were found (Table 1). Interestingly, 20% (group 1) vs. 60% (groups 2) become castrate resistant (CRPC), p<0.0001 and the time to reach CRPC state was much shorter in group 2 (33.5 months) vs. group 1 (57.9 months), p=0.05. Additionally, 60% of group 2 patients vs. 32.5% of group 1 patients developed metastasis, p=0.014. Lastly, median survival of 193 months for group 2 patients with no median survival for group 1, Log Rank test p=0.023. Multivariable logistic regression analysis demonstrated that secondary Gleason score of 5 (compared to 3) and %fPSA>0.15 predicted CRPC status (OR 11.63, CI 95% 1.38-97.4, p=0.024, OR 7.99, CI 95% 2-31.95, p=0.003, respectively). Conclusions: %fPSA>0.15 in the setting of BCR confers a more aggressive disease, manifesting in a faster development of CRPC, metastasis and death. Our findings suggest a reversal in the significance of % fPSA values in BCR patients, and should be validated in larger cohorts. [Table: see text]
Radium-223 retreatment in an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases: 2-year follow-up.
Authors: Sartor A. Oliver , Heinrich Daniel , Mariados Neil , Méndez-Vidal María José , Keizman Daniel , Thellenberg Karlsson Camilla , Peer Avivit , Procopio Giuseppe , Frank Stephen Jay , Pulkkanen Kalevi , Rosenbaum Eli , Severi Stefano , Trigo Perez Jose Manuel , Trandafir Lucia , Wagner Volker Jean , Li Rui , Nordquist Luke T.
Published: February 2018

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Background: Radium-223 (Ra-223) treatment (tx) is indicated for patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) (6 × 55 kBq/kg IV injections [inj]; 1 inj q4wk). Early results of an international, open-label, phase 1/2 study (NCT01934790) showed that re-treating pts with Ra-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from a 2-year follow-up. Methods: Pts with CRPC and bone mets who completed 6 initial Ra-223 inj with no disease progression in bone and later progressed were eligible for Ra-223 re-tx (6 additional Ra-223 inj), provided that hematologic parameters were adequate. No concomitant cytotoxic agents were allowed; other concomitant agents (eg, abiraterone, enzalutamide) were allowed at investigator discretion. The primary objective was safety. Exploratory objectives were time to radiographic bone progression, radiographic progression-free survival (rPFS), overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-tx start. Pts will be followed for safety up to 7 years after last Ra-223 dose; an active 2-year follow-up evaluated exploratory objectives. Safety results from the active follow-up period and updated efficacy are reported. Results: 44 pts were re-treated with Ra-223; 29 (66%) completed all 6 inj (median number inj = 6). 34 (77%) of 44 pts entered active follow-up, during which no new safety concerns were noted. One new primary malignancy was reported (basal cell carcinoma). There were no serious drug-related adverse events. 19 (43%) of 44 pts had an rPFS event (radiographic progression or death); median rPFS was 9.9 months. Only 5 (11%) of 44 pts had radiographic bone progression; median time to radiographic bone progression was not reached. Median OS was 24.4 months. Median time to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Conclusions: Re-treating with Ra-223 was well tolerated in this select pt population, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up. Clinical trial information: NCT01934790.