bluuebunny/crossref_metadata_2025 huggingface dataset:
Referral of early onset renal cell carcinoma for clinical cancer genetic assessment.
Authors: Corrigan Lynda , McDevitt Trudi , Green Andrew J. , Barton David , Gallagher David J.
Published: February 2017

613

Background: Approximately 1-8% of renal cell carcinomas (RCCs) are associated with inherited predisposition. No consensus referral guideline exists for genetic assessment for RCC. Early age of onset, the presence of a family history and type II papillary RCC should trigger clinical genetics referral. We investigated the pattern of cancer genetics referral for early-onset RCC in Ireland. Methods: The number of patients with RCC diagnosed under the age of 50 between 2005 and 2013, was obtained from the National Cancer Registry of Ireland. RCC was defined by the WHO/IARC Classification. The number of patients referred for genetic work-up with RCC < 50 years of age was ascertained from The National Centre for Medical Genetics. Individuals unaffected by RCC but with a family history of RCC were excluded. The database was searched using the following search terms: Von Hippel-Lindau (VHL), Birt-Hogg-Dube (BHD) and RCC; and the clinical reason for referral recorded. Results: 580 patients were diagnosed with RCC below the age of 50. 71 percent were between 40 and 49 years of age (n=410). 52 patients were referred to The National Centre for Medical Genetics. Indications for referral are listed in Table 1. 7 patients were referred for a diagnosis of RCC < 50 years of age. The average age of these patients was 37.8 years. Three of the referrals were for early age of onset of RCC; two referrals were made for early age of onset with a family history of RCC; and two with early onset RCC and bilateral RCCs. This represents a referral rate of approximately 0.01% for early onset RCC in Ireland. Conclusions: Most early onset RCC is not referred for clinical cancer genetics assessment. The heritability of RCC is incompletely understood. Improved referral patterns, increased clinical genetics assessment and a better understanding of the genetic aetiology of RCC may have preventive and therapeutic implications for this disease. [Table: see text]
A multivariate analysis of prognostic factors from assure (E2805): Adjuvant sorafenib or sunitinib for unfavorable renal carcinoma.
Authors: Haas Naomi B. , Manola Judith , Uzzo Robert G. , Flaherty Keith , Pins Michael , Messing Edward M. , DiPaola Robert S.
Published: February 2017

618

Background: Previous post-surgical prognostic nomograms for clear cell RCC are based upon TNM stage, PS, Fuhrman grade, and sometimes presence of necrosis. 1943 patients (pts) with locally advanced renal cell carcinoma (RCC) participated in the ASSURE trial of one year of sunitinib daily for 4 wks of a 6 wk cycle, sorafenib daily, or placebo, then treated for up to 9 cycles. Of these, 1541 pts had clear cell predominant features. There were no significant differences in DFS (median 5.7 years) between either of the experimental arms and placebo, in the total or clear cell population. We investigated site-reported clinical and surgical factors associated with prolonged DFS. Methods: Patients were staged according to the AJCC 2007 version. Factors considered in addition to those in the final model shown below were age, race/ethnicity, histology, risk category and PS as stratified, and 10 other specific baseline symptoms. A Cox proportional hazards model was built including factors that significantly changed the -2 log likelihood ratio (Collett). Results: Shorter DFS was associated with higher age, stage and Fuhrman grade, male sex, PS > 0, open vs. laparoscopic surgical approach, low hemoglobin and diagnosis based on presence of symptoms. Conclusions: The association of stage, grade, age, and PS with outcome confirms previous analyses in resectable disease. The same factors which predict outcome in metastatic disease now clearly confer relapse risk in the postoperative setting. Clinical trial information: NCT00326898. [Table: see text]
Utilization and contemporary results of renal mass biopsy.
Authors: Cahn David , Lim Caitlin , Parsons Rosaleen , Ristau Benjamin T. , Kutikov Alexander , Chen David Y. T. , Greenberg Richard Evan , Viterbo Rosalia , Smaldone Marc C. , Uzzo Robert G.
Published: February 2017

623

Background: Renal mass biopsy (RMB) for localized renal masses (RM) is being re-evaluated to improve risk stratification and minimize morbidity from over-treatment. We review our institutional experience with RMB to identify performance characteristics and highlight opportunities to improve management. Methods: Using our prospectively maintained database, we identified patients who underwent core RMB +/- fine needle aspiration (FNA). We describe performance characteristics and assess pathologic concordance. Using the University of Michigan (UM) algorithm, we reviewed the potential that RMB influenced therapeutic decision-making. Results: We noted 374 RMBs performed from 1999-2015 (66% within last 5 years). Core RMB (+/- FNA) was performed in 65.2% (244/374) of cases, of which 41% (99/244) underwent surgical resection. Initial core RMB was non-diagnostic in 9% (9/99) of surgical cases and subsequently diagnosed with RCC. RCC diagnosed on core RMB that underwent surgical resection demonstrated histologic and grade concordance of 94.3% and 62.5%. All discordant grades were upgraded at surgery. 11% of all RMB were benign and no surgical intervention occurred. In our cohort, 19% of all RMB patients treated surgically had tumors classified as favorable or intermediate < 2cm using the UM algorithm and might otherwise have been candidates for AS. Conversely, 42% of all surgically treated patients had UM favorable characteristics but had tumors > 4cm and therefore underwent surgical resection based on size criteria in the context of RMB results. Conclusions: RMB is effective in the evaluation of RM with minimal morbidity. Our histologic/grade concordance is consistent with published data and underscores that RMB harbors clinical uncertainties. Clinical management pathways incorporating RMB may decrease over-treatment but also may risk under-treatment based on poor grade concordance. Using the UM algorithm, 30% of lesions in our cohort were AS candidates after RMB (over-treatment risk). Conversely, 18% of surgically treated lesions were UM AS candidates after RMB and upgraded on final pathology, demonstrating the risk of under treatment. RMB may be considered in patients where results would influence clinical decision-making.
Risk of CKD after serial intravenous contrast exposure after nephrectomy for kidney tumors.
Authors: Cherington Chad Christian , Tyson Mark , Castle Erik P. , Ho Thai Huu
Published: February 2017

624

Background: The risk of intravenous contrast induced nephropathy (CIN) is not well described in post-nephrectomy or metastatic kidney cancer. Patients with nephrectomies and tumors of the kidney frequently have CKD and often require serial contrast imaging placing them at risk for CIN. Methods: This is a retrospective review of 292 patients metastatic RCC and/or with partial or radical nephrectomies (PN or RN) for kidney tumors at Mayo Clinic Arizona or Florida from 2010 through 2014. Results: We found 207 patients received at least one contrast scan, of whom 99 had metastatic RCC, 104 had local RCC and 4 had oncocytoma. At baseline (pre-nephrectomy) 41% (46/113) and 15% (11/76) of RN and PN respectively had CKD stages 3-5 and with at least 3 months follow up after both nephrectomy and contrast exposure 61% (68/113) and 33% (25/76) RN and PN developed CKD stages 3-5 respectively. The median contrast exposure scans were 4 (range 1-30 scans) with a median follow up of 26 months (range 1-96 months). In all patients with at least one contrast exposure, the median change in creatinine and GFR from baseline was 0.2 mg/dL and 8 ml/min respectively. Excluding those with bilateral nephrectomy there were 8 (8/207 = 4%) CIN events, 6/113 had a radical nephrectomy and 2/76 with 1 partial nephrectomy and 1 aborted nephrectomy (P value 0.37). Of these patients 5 (5/99 = 5%) had metastatic RCC and 3 (3/104 = 3%) local RCC. The median contrast exposure scans for patients with CIN were 8 (range 3-12) and median follow up was 31 months (range 4-47 months). Three patients all with metastatic RCC developed acute kidney injury from CIN requiring dialysis and died of complications in part related to CIN during that hospital stay or soon after. Two other patients developed CKD stage III after CIN events and 3 patients (including the one with a partial nephrectomy) showed no significant change in GFR after CIN. Conclusions: In this retrospective analysis, CIN after nephrectomy or metastatic RCC contributed to acute renal failure with 3 deaths and 2 patients developing CKD stage III. Further analysis is required to determine what risk factors for CIN in this population.
Comparisons of outcomes for patients with high-risk prostate cancer treated with brachytherapy, external beam radiation, or radical prostatectomy.
Authors: Ciezki Jay P. , Singh Harguneet , Reddy Chandana A. , Campbell Steven C. , Ulchaker James , Angermeier Kenneth , Stephenson Andrew J. , Tendulkar Rahul D. , Stephans Kevin L. , Klein Eric A.
Published: February 2017

63

Background: There is no consensus on how to best treat patients (pts) with high-risk prostate cancer. Methods: The outcomes for 2,736 high-risk prostate cancer pts treated with radical prostatectomy (RP), external beam radiotherapy (RT), and I-125 brachytherapy (BT) at a single institution from 1996 to 2012 were reviewed. The majority of RT pts were treated prior to 2002 because of our preference for RP and BT over time. High-risk was defined per the NCCN criteria. The outcomes assessed were biochemical failure (bF), clinical failure (cF), and prostate cancer mortality (PCM). Results: The distribution by treatment was RP 54%, RT 27%, and BT 19%. The median follow up for all pts was 4.6 years (y) (range 0.1-19.5): 3.8 y (0.1-18.7) for RP, 7.7 y (0.1-19.4) for RT, and 4.1 y (0.1-16.8) for BT pts. No patient received RT+BT, and 44% received androgen deprivation therapy (ADT). On multivariable analysis (see table) RP pts were at higher risk for bF vs. RT; BT pts and RT pts were at higher risk for cF vs. RP; and RT pts were at higher risk for PCM vs. RP. All multivariable analyses were adjusted for clinical stage, biopsy Gleason score, pre-treatment PSA, and duration of ADT. Conclusions: RP is associated with worse bF but better cF and PCM. There is no difference between BT and RT for bF, cF, or PCM while BT and RP had similar PCM. These outcomes may be a result of selection bias or differences in follow up time among the three treatment arms so no demonstration of modality superiority is possible. [Table: see text]
Association of chronic baseline prostate inflammation with lower tumor grade in men with prostate cancer on repeat biopsy.
Authors: Moreira Daniel M. , Nickel J. Curtis , Andriole Gerald L. , Castro Ramiro , Freedland Stephen J.
Published: February 2017

75

Background: We have previously shown that chronic baseline prostate inflammation in an otherwise benign biopsy was associated with lower risk of prostate cancer in repeat prostate biopsies and lower tumor volumes for those who are diagnosed with cancer. In the present study, we evaluated whether baseline acute or chronic prostate inflammation among men with initial negative biopsies for prostate cancer was associated with cancer grade at the 2-year repeat prostate biopsy. Methods: Retrospective analysis of 889 men 50-75 years-old with negative baseline prostate biopsy and positive 2-year repeat biopsy for prostate cancer in the REDUCE study. Acute and chronic prostate inflammation (coded as present or absent) and cancer grade were determined by central pathology. The association of inflammation in baseline biopsies with 2-year repeat biopsy cancer grade (low-grade: Gleason scores 2-6 vs. high-grade: Gleason scores 7-10) was evaluated with t test, chi-squared test and logistic regression controlling for age, race, body-mass index (BMI), digital rectal exam (DRE), prostate volume, baseline pre-study PSA and treatment (dutasteride or placebo). Results: Chronic, acute inflammation and both were detected in 533 (60%), 12 (1%) and 85 (10%) baseline biopsies, respectively. Presence of acute and chronic inflammations were significantly associated with each other (P < 0.001). Patients with chronic inflammation had significantly larger prostates (P < 0.001). Both types of inflammation were unrelated to race, BMI, PSA or DRE. At 2-year biopsy, a total of 621 (70%) tumors were low-grade and 268 (30%) tumors were high-grade. In both uni- and multivariable analyses, men with baseline chronic inflammation had significantly less high-grade tumors (univariable OR = 0.64, 95% CI = 0.47-0.87, P = 0.004; multivariable OR = 0.68, 95% CI = 0.50-0.93, P = 0.016) than those without baseline chronic inflammation. Baseline acute inflammation was not associated with tumor grade. Conclusions: Among men undergoing repeat prostate biopsy 2 years after a negative baseline biopsy who all had cancer on the follow-up biopsy, the presence baseline chronic inflammation was associated with lower prostate cancer grade.
Modeling severe late rectal bleeding: Results on a large pooled population of prostate cancer patients.
Authors: Cicchetti Alessandro , Rancati Tiziana , Ebert Martin , Fiorino Claudio , Kennedy Angel , Joseph David John , Denham James William , Vavassori Vittorio , Fellin Giovanni , Valdagni Riccardo
Published: February 2017

82

Background: To develop a model for grade 3 (G3) late rectal bleeding (LRB) after radical radiotherapy (RT) for prostate cancer, in a pooled population from 2 large prospective trials: Airopros0102 (Fellin RO2014) and TROG 03.04 RADAR (Ebert IJROBP2015). Methods: Both trials included patients (pts) treated with 3DCRT at 66-80Gy, conventional fractionation. Planning data were available for all pts, G3 LRB was prospectively scored using the SOMA/LENT, with a minimum follow-up of 3 years. Rectal dose-volume histograms were reduced to Equivalent Uniform Dose (EUD) calculated with volume parameter n derived by 3 studies: n=0.06 (Rancati RO2004), n=0.05 (Rancati RO2011) and n=0.018 (Defraene IJROBP2011). EUD was inserted into multivariable logistic regression (MVL) together with clinical and treatment features. Irradiation of seminal vesicles (SV), irradiation of pelvic nodes, hormonal therapy, hypertension, previous abdominal surgery (SURG), use of anticoagulants, diabetes, cardiovascular diseases and presence of acute toxicity were considered as potential dose-modifying factors. Goodness of fit was evaluated with Hosmer Lemeshow test (HL), calibration through calibration slope and AUC was used for discrimination power. Results: 1,337 pts were available: 708 RADAR and 669 Airopros. G3 LRB was scored in 95 pts (7.1%): 62 RADAR and 33 Airopros. EUD calculated with n=0.05 was the best dosimetric predictor for G3 LRB. A 4-variable MVL model was fitted including EUD (OR=1.07 p=0.16), SV (OR=4.75 p<0.001), SURG (OR=2.30 p=0.02) and cardiovascular disease (OR=1.42 p=0.18). AUC=0.63, calibration slope=0.99 (R^2=0.89), p for HL=0.43. Inclusion of acute toxicity (OR=2.34 p<0.001) slightly improved AUC (0.65), confirming a possible role of consequential injury. Conclusions: EUD with n=0.05 was predictive of G3 LRB in this pooled population, confirming the importance of sparing the rectum from high doses. Irradiation of seminal vesicles together with the presence of cardiovascular disease and previous abdominal surgery were relevant dose-modifying factors highly impacting the incidence of G3 LRB. The study was funded by: AIRC IG16087, Fondazione Monzino, NHMRC (300705, 455521, 1006447)
The REQUITE Project: Validating predictive models and biomarkers of radiotherapy toxicity to reduce side-effects and improve quality of life in cancer survivors.
Authors: Valdagni Riccardo , Appanvel Anusha , Botma Akke , Webb Adam , Azria David , Burr Tom , Chang-Claude Jenny , Davidson Susan , Elliot Rebecca M. , Gutierrez-Enríquez Sara , Johnson Kerstie , Lambin Philippe , Rancati Tiziana , Rosenstein Barry , Ruysscher Dirk De , Talbot Chris , Thierens Hubert , Vega Ana , Wenz Frederik , West Catharine
Published: February 2017

85

Background: To present the REQUITE project (Validating Predictive Models and Biomarkers of Radiotherapy (RT) toxicity to reduce side-effects and improve quality-of-life in cancer survivors) and first results on the enrollment and acute toxicity (tox) of prostate cancer (Pca) patients (pts). Methods: The European Union funded REQUITE project involves centers in Europe and the USA. The main objectives of the project are to: carry out a multicentre, cohort study collecting blood samples, standardized epidemiology and treatment data, longitudinal side-effect and quality of life data (before and after treatment, years 1 and 2); produce a centralized database and biobank of DNA for 5,300 patients; validate clinical/dosimetric predictors of RT tox and incorporate biomarker data. The project focuses on cancers of the breast, lung and prostate. For PCa the primary endpoint is rectal bleeding at 2 years. Results: A centralized database was established for data collection, including storage of complete dosimetric information in DICOM RT format. Enrollment started in April 2014 and will end in August 2018. In the first 16 months 909 PCa pts were enrolled: 10% low risk, 33% intermediate and 57% high risk. 63% pts received exclusive RT (neoadjuvant hormone therapy in 62%) and 37% post-prostatectomy; 97% external beam RT (prescription doses: 60-85Gy, 2Gy equivalent, alpha/beta=3Gy), while 3% received brachytherapy. Data on acute tox at RT end (measured by CTCAE 4.03) are available for 496 pts. 79 G2-G3 GI tox were reported, with proctitis and diarrhea having the higher prevalence (45 and 30 events respectively). 74 pts exhibited G2-G3 GU tox, with 34 pts reporting multiple symptoms and frequency and urgency having the higher prevalence (43 and 30 events respectively, 25 pts both). Conclusions: REQUITE is proving the feasibility of a prospective standardized collection of epidemiological/clinical/dosimetric/toxicity data coupled to centralized storing of biological material. Meanwhile a large database is being created, which will be of value also for future research in the field of radioinduced side effects. REQUITE is funded by a European Union FP7 grant (601826).
MRI-US fusion targeted biopsy results in patients with a history of a prior negative biopsy.
Authors: Nawaf Cayce , Lu Amanda , Rosoff James , Weinreb Jeffrey , Schulam Peter , Humphrey Peter , Levi Angelique , Sprenkle Preston
Published: February 2017

90

Background: Patients with an elevated PSA but negative prostate biopsy present a diagnostic and management dilemma. We evaluated the capability of multi-parametric (MP) MRI and MRI-USG Fusion prostate biopsy to detect clinically significant (CS) prostate cancer in men who have had a prior negative 12-core standard biopsy. Methods: Between 12/2012 and 06/2015, 374 men with an indication for prostate biopsy underwent pre-biopsy mpMRI followed by 12-core standard trans-rectal mapping biopsy (Mbx) and MRI-Ultrasound fusion targeted biopsy (Tbx) of lesions identified on mpMRI. The combination of Mbx and Tbx, when both occurred, constitutes a fusion biopsy (Fbx). Men who underwent both Mbx with or without Tbx using the Artemis/Pro-Fuse system with a previous biopsy but no diagnosis of prostate cancer were included. Patients without a lesion on MRI underwent Mbx only. Maximum Gleason scores (GS) was assigned on a per patient basis with Mbx GS available for all patients in the cohort and Tbx GS available only for patients with a lesion visible on MP-MRI. CS cancer was defined as GS ≥ 3+4. GS per patient was compared by chi-square and McNemar’s test. Results: 138 men (mean age = 64.0, mean psa = 11.6) met inclusion criteria. Fbx cancer detection rate in this population was 42%. 17 men (12%) were missed by Mbx but picked up on Tbx. Of these 17 men, 13 had Gleason ≥ 7.In comparison, 15 men were missed by Tbx, but only 2 were Gleason ≥ 7. Tbx had a higher rate of detection of CS cancer than Mbx, but this did not reach statistical significance (86% vs 68%, p = 0.09). MRI suspicion level correlated with the detection of CS cancer (p = 0.012). None of the 20 men with a negative MRI had GS ≥ 7 cancer detected on Mbx. The number of prior negative biopsies was not related to the likelihood of finding CS cancer on Fbx (p = 0.47). Conclusions: MRI suspicion score predicts detection of CS prostate cancer when paired with MRI-USG Fbx of the prostate, with a negative MRI correlating with no evidence of CS cancer on biopsy. MRI is a biomarker in this population that may, with more corroborative data, allow for men with a negative MRI to avoid repeat biopsies. [Table: see text]
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.
Use of recommended post-treatment services for adolescent and young adult Hodgkin lymphoma survivors.
Authors: Hahn Erin Elizabeth , Wu Yi-Lin , Garcia Delgadillo Jazmine , Munoz-Plaza Corrine E.
Published: February 2017

107

Background: Adolescent and young adult (AYA) Hodgkin lymphoma survivors are at high risk for long-term and late effects. Post-treatment guidelines are available from the National Comprehensive Cancer Network (NCCN) and others; however, adherence to these guidelines is unknown. The purpose of this study was to identify AYA Hodgkin survivors from an integrated health care system and examine use of post-treatment services. Methods: We identified patients diagnosed between 2000 and 2010, ages 15 to 39. We identified use of NCCN recommended services (oncology visits, labs, CT) and non-recommended services (PET scan, CT after first year). Multivariate logistic regression was used to identify associations between receipt of recommended services within first 12 months post-treatment (oncology visits, labs, CT) and patient (gender, race/ethnicity) and cancer characteristics (stage, diagnosis age, diagnosis year). Results: We identified 354 patients (see table). Almost all had recommended oncology visits within the first 5 years (96%); 70% received recommended labs. Two-thirds received a recommended CT scan within 12 months post- treatment. However, 47% received a non-recommended CT in year 2 and 35% in year 3, and 33% received a non-recommended PETs. Overall, 48% received all recommended care within the first 12 months. Diagnosis year was significant in regression, with those diagnosed 2000-2005 less likely to receive recommended care than those diagnosed 2006-2010 (OR = 0.007, p < .0001). Conclusions: Less than half of patients received recommended care within the first year post-treatment. These results will inform development of effective programs to meet survivors’ needs. Next steps include exploring risk-stratified patterns of care in long-term survivors. [Table: see text]
Our act on fertility preservation for young breast cancer patients in our single institute.
Authors: Kojima Yasuyuki , Tsuchiya Kyoko , Nishijima Chie , Suzuki Nao , Tsugawa Koichiro
Published: February 2017

109

Background: Along with increasing number of newly diagnosed Japanese breast cancer patients, the number of breast cancer survivors in reproductive age is also increasing. Among newly diagnosed Japanese breast cancer patients, 3182(6.6%) are under age 40 in 2011, which was 1610 in 2006. In our institute, we have been cooperating with gynecologists and providing fertility preservation program since 2010. Our aim is to access our team management, clinical impact and outcome of fertility preservation among young breast cancer patients in our institute. Methods: A patient, 1)without distant metastasis, 2)systemic chemotherapy and/or hormonal therapy planned, 3)within reproductive age and 4)willing to preserve fertility, will be referred to oncofertility clinic. Chart review was done retrospectively. Results: Ninety-five patients had consultation to the oncofertility clinic between April 2010 and April 2015. The average age at consultation was 34.1(range 22-44). Almost all patient had invasive cancer; cStage0:4%, cStageI:31%, cStageII:53%, cStageIII:11%. Fifty-five percent had estrogen receptor (ER) positive/HER2 negative, 31% had ER positive/HER2positive, 2% had ER negative/HER2 positive and 12% had ER negative/HER2 negative breast cancer. Forty-five had counseling without any procedure, 22 underwent ovarian tissue cryopreservation, 17 underwent embryo cryopreservation and 8 underwent oocyte cryopreservation. Because observation period is still short, we haven’t had any case that got pregnant or delivered, yet. Conclusions: The number of patient who choose to underwent fertility preservation is increasing. We have actually started facing proposition, when we shall lay aside adjuvant therapy and let them plan to be conceived. Taking risk into account, we are now evaluating the safety of cancer treatment and outcome of each procedure which undergone multidisciplinary deliberate decision-making process.