bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of subsequent metastasis on survival in Medicare patients with prostate cancer.
Authors: Li Tracy , Shore Neal D. , Mehra Maneesha , Todd Mary Beth , Saadi Ryan , Leblay Gaetan , Griffiths Robert 
Published: February 2017

94 Background: This study assessed the impact of subsequent metastasis on survival in Medicare prostate cancer (PC) patients initially diagnosed with locoregional disease. Methods: Using data from the United States Surveillance, Epidemiology, and End Results (SEER) cancer registry linked to Medicare claims, we identified patients diagnosed with locoregional PC between 2000 and 2011, age ≥ 66 at diagnosis, and who first had a diagnosis of metastasis ≥ 4 months after PC diagnosis (cases). Cases were matched to controls (patients without metastasis) in a 1:4 ratio to assess the incremental impact of developing metastasis. For each control, the timeline to develop metastasis was matched to the cases. Kaplan-Meier (K-M) analysis was used to compare all-cause, cancer-specific, and other-cause mortality between cases and controls. Cox proportional hazards regression was used to adjust for other factors associated with all-cause mortality. Results: There were 10,370 cases and 39,200 controls. Mean age at baseline was 79 years in each group. Among the cases, the median time to first metastasis was 37 months, 85% had bone metastasis, and the median survival time (months) after metastasis was 18 months compared to 118 months for controls (P < 0.0001: Log-Rank). In K-M analysis, metastasis was associated with significantly (P < 0.0001: Log-Rank) higher all-cause, cancer-related, and other-cause mortality. In multivariable survival analysis, metastasis was associated with increased all-cause mortality (HR = 4.6, 95% CI = 4.4-4.7, P < 0.0001). High risk disease (based on Gleason score, comorbidity Index, and performance status) and delayed diagnosis of metastases were associated with worse survival. Conclusions: Development of metastasis in elderly PC patients diagnosed with locoregional disease significantly increases mortality.
High dose rate brachytherapy as monotherapy for localized prostate cancer: Our initial experience.
Authors: Challapalli Amarnath , Masson Susan , Humphrey Pauline , Bamisaye Frances , Jacobs Petra , French Chris , Bahl Amit 
Published: February 2017

e626 Background: High dose rate (HDR) brachytherapy is an attractive treatment option for localized prostate cancer (CaP) as it allows for safe dose escalation and exploits the radiobiological advantage of using a high dose/fraction. We evaluate our early experience in using HDR monotherapy for localized CaP. Methods: Forty patients with low- to intermediate-risk CaP were treated from October 2013-July 2015. Patients had catheters placed transperineally under spinal anaesthesia, using transrectal ultrasound guidance. The clinical target volume [CTV: prostate ± seminal vesicles base] was outlined on a planning CT scan with the catheters and template in-situ. The CTV was grown by 3mm isotropically to obtain the planning target volume (PTV). The catheters were reconstructed and plan optimised according to pre-set dose constraints [DC]. Dose delivered was 19Gy/one fraction. Toxicity was assessed using RTOG criteria. Results: A range of volumes were implanted (20–120 cc, median: 37.5), using a median of 17 needles (range 13–20). Satisfactory implants were achieved in patients with volumes>60cc by excluding pubic arch interference on the pre-implant MRI pelvis. All patients were discharged home within 24 hours, with two patients (5%) requiring re-catheterisation. Good dose coverage to the PTV was achieved: median D90 of 20.4Gy (DC>19Gy), V100 of 95.1% (DC≥95%). Urethral and rectal sparing was satisfactory: urethral D10 of 21.23Gy (DC<22Gy), rectal D2cc of 14Gy (DC<15Gy). The median follow-up was 8 (1-22.6) months. Twenty-five patients, with at least 6 months follow-up showed a median PSA reduction of 80%. Thus far, one had biopsy proven recurrence. Only two patients had grade 3 urinary toxicity and one had grade 3 bowel toxicity at 2 weeks, which returned to baseline at 12 weeks. The IPSS score increased at 2-4 weeks after treatment, but returned to baseline after 3 months. Conclusions: Our initial experience with HDR monotherapy for localized CaP confirms this to be safe, with minimal acute complications. It is possible to implant volumes higher than 60cc, if adequate measures are taken. The early efficacy data for 19Gy is also promising.
Effect of FSH supplementation on the GnRH antagonist suppressed growth of PC-3 cell xenografts in nude mice.
Authors: Oduwole Olayiwola , Rawson Phil , Rahman Nafis , Koechling Wolfgang , Huhtaniemi Ilpo 
Published: February 2017

e630 Background: One of the fundamental differences between GnRH agonist and antagonist treatment is the permanent suppression of FSH by antagonist, while a rebound in FSH secretion has been documented upon agonist treatments. To assess the potential beneficial effects of permanent FSH suppression in the hormone ablation treatment of prostate cancer we studied the effect of the GnRH antagonist degarelix in the absence and presence of FSH supplementation on the growth of PC-3 human prostate cancer cell xenografts in nude mice. Methods: Intact (n = 20) and gonadectomized (n = 20) nude male mice were inoculated with 2 x 106PC-3 cells. Half of each group received degarelix treatment at 10 mg/kg body weight s.c. In a second experiment (n = 10/group), degarelix treatment was supplemented with recombinant human FSH at10 IU/kg/day using i.p. ALZET osmotic minipumps. Tumor growth in both experiments was monitored for 4 weeks by external inspection and caliper measurement, after which the mice were sacrificed. Results: The first experiment demonstrated that degarelix treatment significantly reduced tumor growth by 33% and 35%, respectively, in intact and gonadectomized mice as compared to non-treated controls (p<0.0001 for each). In the second experiment, FSH reversed the inhibitory effect of degarelix in intact mice. Conclusions: These results demonstrated that the suppression of PC-3 xenograft growth by GnRH antagonist treatment was completely inhibited by concomitant FSH treatment. The findings prove experimentally the principle that combined FSH and LH suppression by GnRH antagonist could offer an advantage over the isolated LH suppression by GnRH agonist upon prostate cancer treatment. [Table: see text]
MRI response to focal salvage HDR prostate brachytherapy for locally recurrent prostate cancer after external-beam radiotherapy.
Authors: Chung Hans T. , Morton Gerard , D'Alimonte Laura , Loblaw Andrew , Ravi Ananth , Wronski Matthew , Davidson Melanie , Haider Masoom A. 
Published: February 2017

e631 Background: For local recurrence after external-beam radiotherapy, salvage therapy options include surgery, brachytherapy, cryotherapy or high-frequency ultrasound, though there is a significant risk of serious complications (e.g. fistula, incontinence, bladder neck contracture). In the meantime, MRI technology has evolved (e.g. DCE and DWI) such that the sensitivity of detecting viable cancer within the prostate is now more than 70%. Therefore, we initiated a pilot study of focal salvage HDR prostate brachytherapy in patients screened with a MRI with the hypothesis that focal treatment, rather than whole gland, would lead to less complications but similar local control. The MRI response is presented here. Methods: This study was approved by the institution’s research ethics board. Eligible patients included: biopsy-confirmed local recurrence > 30 months after completing XRT, MRI demonstrating solitary recurrence confined to the prostate, negative metastatic workup, IPSS < 15, post-XRT PSA < 10ng/mL, prostate volume ≤ 50cc. Salvage ultrasound-based HDR brachytherapy was performed with a prescription dose of 27Gy divided over two implants separated by 1 week to the target volume (TV) as seen on MRI with dose constraints to the urethra and rectum. All MRI scans were completed with 3T and included T2W, DCE and DWI. Lesions suspicious for cancer were scored using PI-RADS methodology pre-brachytherapy, and using a 5-point scale post-brachytherapy. Results: Fifteen patients were accrued. Thus far, 6 of 15 patients have completed a post-brachytherapy MRI (median 530 days; range 307-653). The baseline MRI characteristics of these 5 patients include: PI-RADS 4 (n = 1), 5 (n = 4), not specified (n = 1); median size 9 mm (range 7-9); T2 (n = 5) and T3a (n = 1); median prostate volume 28mL (20-63). In the post-brachytherapy MRI, the treated intraprostatic lesion no longer showed areas of cancer in 5 patients. Two patients developed a new focus of cancer in the prostate. Patients were not routinely biopsied after brachytherapy. Conclusions: Preliminary data from MRI suggests that there is a treatment response in most patients after focal salvage brachytherapy. Clinical trial information: NCT01583920.
68Ga-PSMA PET/CT imaging predicting intraprostatic tumor extent prior to radical prostatectomy in patients with prostate cancer.
Authors: von Klot Christoph A. J. , Merseburger Axel S. , Kuczyk Markus A. , Schmuck Sebastian , Bengel Frank M. , Derlin Thorsten 
Published: February 2017

e632 Background: The performance of gallium Ga 68 (68Ga)-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) shows promising results with regard to lymph node detection even at low prostate specific antigen (PSA) levels in patients with biochemical recurrence after curative therapy for prostate cancer. In this study we evaluate the usefulness of PSMA-PET/CT for the evaluation of intraprostatic tumor extent prior to radical prostatectomy. Methods: In total 15 patients with prostate cancer underwent a 68Ga-PSMA-PET/CT before surgical treatment. All patients received either open or laparoscopic radical prostatectomy. Intraprostatic tumor extent was assessed on PET/CT. The peak standardized uptake value (SUV) was correlated with final whole gland histopathology including Gleason grade, lobe infiltration, TNM stage and seminal vesicle invasion. Results: Mean SUV over all patients was 10.64 ±9.19. Median Gleason score was 7. The distribution of TNM stage 2a, 2b, 2c, 3a, 3b, 4 was 0, 2, 6, 5, 2 and 0 patients. Mean intraprostatic SUV for patients with organ confined vs. extraprostatic tumor on histopathology was 6.3 and 15 respectively (p = 0.043). Mean SUV for patients with a Gleason score of ≤ 7a and > 7a was 6.2 and 13.5 (p = 0.046). Sensitivity and specificity for identifying tumor invasion of a prostate lobe was 84.6% and 75% (Positive and negative predictive value (PPV, NPV) for prostate lobe invasion were 95.7% and 42.9%). Sensitivity and specificity for seminal vesicle invasion were 50% and 100% (PPV 100%, NPV 96.6%). Conclusions: These early results need to be further validated in a larger cohort.
Effect of ProSpare (PS), a rectal obturator, on inter- and intrafraction prostate motion and anorectal doses in prostate radiotherapy (RT).
Authors: Murray Julia , McNair Helen , Alexander Emma , O'Shea Tuathan , Thomas Karen , Nill Simeon , Gulliford Sarah , Dearnaley David P. 
Published: February 2017

e633 Background: PS is a single use, self-insertable endorectal device designed as a daily image-guidance tool for prostate cancer RT. Rectal filling is a significant factor in prostate motion. We investigated the effect of PS on inter- and intrafraction prostate motion and its effect on anorectal dosimetry. Methods: 19 patients with localized prostate cancer were randomized to receive prostate RT with PS either in the 1st or 2nd half of treatment. For each patient two planning CT scans were acquired, without and with PS. Contours were delineated by one physician and planned with a forward multi-segment technique to a dose of 74Gy/37F. Dose surface histograms were created (VODCA). In all patients, 3 electromagnetic transponders (EM) were implanted into the prostate and daily online image-guided RT was performed using either cone-beam CT (Elekta) or Calypso–based localization with tracking. Interfraction systematic (Σ) and random (σ) errors were estimated for bone matching without and with PS using EM position as reference. CTV-PTV margins were generated using the Van Herk formula. In-house code was used to analyse intrafraction motion recorded by Calypso of the EM centroid in the RL, SI and AP planes for individual fractions. A 2-way ANOVA test (SPSS v22) was used to determine if PS had an effect on maximal intrafraction prostate displacement. Results: See Table. Conclusions: PS affects the dosimetric pattern to the anal canal and rectum and this may impact GI toxicity. Also, PS stabilizes the prostate, which could enable reduced planning margins. PS will now be assessed in post-prostatectomy RT within a randomized controlled trial, POPS. Clinical trial information: 11814. [Table: see text] [Table: see text] [Table: see text]
Understanding the mechanism of warfarin-mediated PC prevention.
Authors: Jones Jeremy , Tew Ben Yi , otto-Duessel Maya , Tong Tommy , Kalkum Markus , Hong Teresa , Liu Xueli , Pal Sumanta K. 
Published: February 2017

e635 Background: Multi-institution retrospective trials have shown that prolonged use of warfarin reduces the risk of prostate cancer (PC), an effect that is not observed for other cancers. The anti-coagulant warfarin prevents the gamma-carboxylation (gla) of target proteins by interfering with the vitamin K cycle through its inhibition of the vitamin K epoxide reductase (VKOR). Most known gla proteins are found in the clotting cascade, but here we investigate the role of gla of the androgen receptor (AR) and other warfarin-mediated effects in the prevention of PC by warfarin. Methods: We treated mice with warfarin and performed RNA-seq on prostate tissues. We used immunoprecipitation (IP) followed by mass spec sequencing to identify gla sites on AR. We used cell culture models to investigate the role of AR-gla and other pathways identified by RNA-seq data in the mechanism of action of warfarin. Finally, we sequenced a SNP in VKOR and performed IHC to detect VKOR expression in prostatectomy tissues in an institutional series. Results: RNA-seq data show alteration of several pathways in warfarin-treated mouse prostates, including AR signaling, hormone and lipid synthesis, and genes known to affect PC (e.g. SPINK1). Mass spec shows that AR is gla’d at amino acid 2E, which is known to be mutated in partial androgen insensitivity syndrome patients. Warfarin inhibits AR conformation change and transcriptional activity in benign (non-cancerous) prostate cells. VKOR knock-down recapitulates effects of warfarin treatment, suggesting an on target effect of the drug. Mutation of the AR-gla site has modest effects in benign prostate cells. In a small series of patients, we found that one allele of a VKOR SNP is found at a significantly higher rate in PC patients than expected. We also found that VKOR is highly expressed in normal human prostate epithelia but is lost in cancerous tissue, a pattern of expression that is unique to PC. Conclusions: Warfarin, likely through its ability to control AR-gla, inhibits AR transcriptional activity. The relative contribution of modest AR inhibition and the effect on other pathways must be investigated to determine how warfarin reduces the risk of PC and to identify optimal drug targets for development of chemopreventative therapeutics.
Cancer survivorship algorithms as clinical tools for primary care providers.
Authors: Palos Guadalupe R. , Gilmore Katherine Ramsey , Lewis-Patterson Paula A. , Rodriguez Maria Alma 
Published: February 2017

100 Background: Clinical decision tools (CDTs) such as survivorship algorithms may be valuable resources for primary care providers who provide post-treatment care for cancer survivors. Our objective was to assess providers’ perceptions, adoption, and satisfaction with clinical practice algorithms tailored to site-specific cancer survivorship clinics. Methods: Eligible providers were those assigned to one of 9 site-specific survivorship clinics, (breast, colorectal, genitourinary, gynecology, head and neck, lymphoma, melanoma, stem cell transplant, and thyroid). Potential respondents were invited to participate by emails. Voluntary return of the survey indicated a provider’s informed consent. Providers had the choice to participate by clicking on a link embedded in an email. Once the link was activated, the user was taken to a 10-item survey with questions asking about the usability, awareness, and satisfaction with the algorithms specific to their clinic. Descriptive statistics (i.e. frequencies and percentages) were used to summarize the responses. Results: Of 35 providers assigned in the survivorship clinics, 18 responded resulting in a 51% response rate. The majority of respondents (94.4%) were aware of the survivorship algorithms specific to their clinic. Over 75% reported using the algorithms occasionally (16.7%), frequently (33%) and always (33.3%). The major barrier to using the algorithms was a lack of awareness on to access the algorithms. Over half of the providers (55.6%) preferred using the digital versions of the algorithms. 68% strongly agreed the algorithms were practical to use and implement in their clinical setting. The majority of providers’ reported being satisfied (62.5%) or very satisfied (25.0%) with the algorithms tailored to their site specific clinic. Conclusions: Survivorship practice algorithms were perceived as useful clinical resources to deliver coordinated care to cancer survivors with diverse cancer diagnoses. Future work is needed to determine the impact of the algorithms on providers’ practice with cancer survivors.
Primary care provider engagement about breast cancer care during treatment: Results from the iCanCare Study.
Authors: Wallner Lauren P. , Abrahamse Paul , Friese Christopher Ryan , Katz Steven J. , Hawley Sarah T. 
Published: February 2017

101 Background: Collaborative care between cancer specialists and primary care providers (PCP) ensures high quality cancer care. Yet, little is known about patient’s perspectives about the level of PCP engagement in and communication about breast cancer (BC) care during treatment. Methods: A weighted random sample of newly diagnosed breast cancer patients in the Georgia and Los Angeles SEER registries were surveyed approximately 6 months after diagnosis (expected final N = 2600, 70% current response rate). PCP BC engagement and communication were defined using 2 outcome measures (categorized as less (never/rarely) vs. more (sometimes/often/always)): how informed the respondent’s PCP was about BC treatment and how often respondents talked with their PCP about their BC care visits. Overall PCP quality was assessed by averaging patient responses (5 categories, never to always) to 5 questions: ease of access to PCP (3 questions) and PCP’s awareness of patient values (2 questions) and categorized as high ( ≥ 4), moderate (3) and low ( < 3). The associations between patient factors and PCP quality with BC engagement and communication were evaluated using multivariable logistic regression. Results: In a preliminary sample (N = 2054), the majority of women reported high PCP quality (63%), high PCP BC engagement (65%) and communication (68%). (Table) Women who reported less PCP BC engagement were more likely to report low PCP quality (OR: 15.7, 95%CI: 9.5, 25.9;) and chemotherapy use (OR: 1.3, 95%CI: 1.1, 1.6), adjusting for age, race, insurance, comorbidities and PCP continuity. The results were similar for PCP communication. Conclusions: Patient perceptions of PCP quality, engagement and communication during BC treatment are high for most women with BC. However, there remains opportunity for improvement in both, as many women report poor engagement and communication despite perceiving high quality primary care. Targeting these patients and their clinicians may be particularly effective in interventions to improve collaborative care in cancer. [Table: see text]
Integrating primary care and cancer care in survivorship: A collaborative approach.
Authors: Sussman Jonathan , McBride Mary L , Sisler Jeffrey , Kim Grace , Game Laura , Ozokwelu Emmanuel , Gingerich Joel Roger , De Rossi Stefanie , Grant Maria 
Published: February 2017

103 Background: Primary care providers (PCPs) have an important role in the provision of survivorship care. While there is evidence to support the feasibility and safety of PCP-led survivorship care, there are gaps in knowledge about how to best integrate providers to support transitions, enhance quality of care, increase system efficiencies, and improve patient and provider satisfaction. Methods: A pan-Canadian study comprised of three projects has been initiated to address three key aspects of care integration, based on a previously described system performance framework. Functional integration will be studied through the evaluation of electronic survivorship care plans using a prospective cohort of breast and colorectal cancer patients with pre and post measures of knowledge, care coordination, and satisfaction. Vertical integration will be evaluated through a series of descriptive case studies to document structures and processes that are currently in place to support PCP re-referral to regional cancer centres. Clinical integration will be studied through the development and evaluation of an interspecialty survivorship training curriculum for oncology and family medicine trainees. Results: Functional integration: Development of an electronic platform for care plan outputs is complete. Two sites in Ontario (ON) and one in British Columbia (BC) have been selected to study the impact on 200 patients and their providers. Vertical integration: Using a study-specific interview guide, 48 semi-structured key informant interviews have been successfully conducted in ON; 15 interviews are planned for Manitoba (MB) and 15 for BC. Clinical Integration: a National Advisory Committee was established and needs assessments were performed with postgraduate program directors, cancer survivors, and trainees using online surveys and focus groups. A blended learning curriculum is being piloted in MB, ON, and BC in 2015. Conclusions: Integrating primary care and cancer care in survivorship requires a collaborative approach that begins in residency, supports PCPs with clear mechanisms for re-entry, and optimizes communication. This study will inform approaches to enhancing provider integration and survivorship care.