bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of nonmetastatic (M0) prostate cancer (PC) patients on continuous androgen deprivation therapy (ADT) in the United States.
Authors: Cetin Karynsa , Li Shuling , Blaes Anne Hudson , Stryker Scott , Liede Alexander , Arneson Thomas J. 
Published: March 2020

4659 Background: ADT is the cornerstone treatment of metastatic PC, but the nature and extent of its use in the M0 setting is less well-described. We sought to estimate the current prevalence of M0 PC patients actively receiving continuous ADT (≥6 months) in the US. Methods: Two point-prevalent cohorts on 12/31/2008 with continuous insurance coverage in 2008 were assembled: men aged 45-64 years (yrs) enrolled in commercial health plans (MarketScan) and men aged ≥67 yrs enrolled in fee-for-service (FFS) Medicare (Medicare 5% sample). Among those with evidence of PC and no evidence of metastases, we selected men who had continuous exposure to gonadotropin-releasing hormone agonists during at least the last 6 months of 2008 or received bilateral orchiectomy prior to 7/1/2008. The number of prevalent ADT users was extrapolated to the entire national commercially insured population aged 45-64 yrs and to the entire Medicare FFS population aged ≥65 yrs using person-level weights. Applying age-specific prevalence estimates to the US Census population on 12/31/2008, we estimated the number of prevalent ADT users in the total US male population aged ≥45 yrs. Results: An estimated 11,935 (95% confidence interval [CI]: 11,310-12,561) commercially insured men aged 45-64 yrs and 115,468 (95% CI: 112,304-118,633) Medicare FFS men aged ≥65 yrs were M0 PC patients actively receiving continuous ADT for ≥6 months on 12/31/2008. Extrapolated to the total US male population aged ≥45 yrs, this estimate was 188,916 (95% CI: 184,104-193,727). Age-specific prevalence (N [95% CI]) on 12/31/2008 is presented in the table. Conclusions: We projected nearly 190,000 US men with M0 PC were actively receiving continuous ADT for ≥6 months at the end of 2008, and the vast majority (91%) of these men were aged ≥65 yrs. Additional work will address timing of initiation, duration, and other aspects of ADT use in this large population of M0 PC patients. [Table: see text]
A first-in-human phase I imaging study using hyperpolarized 1c-13 pyruvate (h-Py) in patients (pts) with localized prostate cancer (l-PCa).
Authors: Harzstark Andrea Lynne , Weinberg Vivian K. , Grycz Krystyna , Hurd Ralph E. , Ardenkjaer-Larsen Jan Henrik , Murray Jonathan , Chen Albert , Ferrone Marcus , Park Ilwoo , Reed Galen , Munster Pamela N. , Small Eric Jay , Carvajal Lucas E. , VanCriekinge Mark E. , Larson Peder E. , Chang Jose , Bok Robert A. , Nelson Sarah J. , Vigneron Daniel B. , Kurhanewicz John V. 
Published: March 2020

4660 Background: Preclinical studies demonstrated that the conversion of h-Py to hyperpolarized 13C lactate (h-lac) is detectable on MRI-spectroscopy and is a useful marker of differentiation in PCa. H-Py MRI provides more than 10,000-fold enhancement in signal to noise ratio (SNR), allowing for rapid detection of metabolic alterations in vivo. Hyperpolarized compounds have not been previously studied in man. Methods: Pts with biopsy-proven untreated l-PCa were enrolled in a phase I study of h-Py MRI. Following a modified 3+3 design, 6 pts were enrolled at each dose level (0.14, 0.28 and 0.43 mL/Kg): 3 to monitor kinetics of h-Py, and 3 to evaluate the spatial distribution of metabolism in PCa and normal prostate (nl-P). An expansion cohort of 15 pts explored the biological variability of metabolism. A dynamic nuclear polarization (DNP) system, the first human system anywhere, generated and delivered 230 mM sterile h-Py. IV injection of h-Py was followed by imaging with a 3T MR scanner with custom transmit and receive coils. Monitoring included EKG, vital signs, and laboratory testing. Results: 31 pts were imaged. 23 pts had Gleason (G) 6, 6 pts G7, and 2 pts G8 PCa. Median age was 63 years (range 45-75); median PSA was 5.9 ng/mL (1.88-20.2). No dose limiting toxicities or >grade (gr) 2 toxicity was observed. Toxicity included: gr 1dysgeusia (6 pts), gr 1 hypokalemia, gr 1 hypocalcemia, gr 1 dizziness, and gr 2 diarrhea (1 pt each). Median time from dissolution of the agent to delivery into patients was 66 seconds (43-88). Signals from h-Py and h-Lac were seen in PCa and nl-P at all doses; 0.43 mL/Kg showed the best SNR and discrimination between PCa and nl-P and was therefore established as the phase II dose. There appeared to be an association between h-Lac levels and PCa grade. Conclusions: H-py metabolic imaging has minimal toxicity and provides the ability to discriminate Ca from nl-P based on increased levels of h-lac. The correlation with grade and changes with therapy require further study.
Response to ketoconazole (keto) or docetaxel (D) following clinical progression on abiraterone acetate (AA) in castrate-resistant prostate cancer (CRPC).
Authors: Aggarwal Rahul Raj , Formaker Carl , Small Eric Jay , Molina Arturo , Ryan Charles J. 
Published: March 2020

4664 Background: Patients (pts) with CRPC treated with keto often experience a rise in serum adrenal androgen levels upon progression and may subsequently respond to more potent adrenal suppression with AA. In contrast, pts treated with AA do not have a rise in serum androgen levels upon progression, and thus may not respond to further androgen synthesis inhibition with keto but require other treatment modalities such as chemotherapy instead. The goal of this analysis is to report the outcomes of pts with CRPC progressing on AA subsequently treated with either keto or D. Methods: Pts with chemotherapy-naïve CRPC were treated on previously reported phase 1 and 2 trials of AA, with doses ranging from 250 to 1000 mg/day. Subsequent treatment following progression on AA was per individual investigator discretion, including treatment with either keto or D. Results: To date, following disease progression on AA, 6 and 14 pts have been subsequently treated with either keto or D respectively. Of the 14 pts treated with D, 11 (79%) had exposure to keto prior to AA. The keto- and D-treated cohorts were similar with respect to other baseline factors, including prior response to AA (4/6 (67%) pts with > 50% PSA decline on AA in keto cohort; 10/14 (71%) pts in D cohort); though pts treated with D were more likely to require opioid analgesics (0 pts in keto cohort; 7 (50%) in D). For pts treated with keto, none experienced a decline in PSA, improvement in bone scan, or an objective response; all had disease progression by 12 weeks. In contrast, for pts treated with D, 10 (71%) had a decline in PSA; 6 (43%) with a > 50% maximum PSA decline. Of 6 pts with measurable disease, 2 (33%) had an objective response. The median time to progression for the D cohort was 129 days (range 60 – 294). Conclusions: Although the cohort size is small, and post-AA therapy was not randomized, these data provide preliminary support for the hypothesis that CRPC progressing on AA is cross-resistant to further androgen synthesis inhibition with keto. Contrary to other reports, prior treatment with AA does not appear to decrease the likelihood of subsequent response to D, but this observation requires prospective validation.
African American race to predict for earlier failure of active surveillance: Results from the Duke Prostate Center.
Authors: Bassett Mitchell , Abern Michael , Banez Lionel Lloyds , Ferrandino Michael , Robertson Cary N. , Inman Brant Allen , Polascik Thomas , Freedland Stephen J. , Walther Philip John , Moul Judd W. 
Published: March 2020

4670 Background: As concerns mount regarding overtreatment and over-diagnosis of prostate cancer (CaP), active surveillance (AS) is increasingly utilized in low risk patients. While African-American (AA) race is associated with adverse outcomes after prostatectomy, its effect on patients managed with AS is not known. Methods: A retrospective review identified 222 patients managed with AS at the Duke Prostate Center from January 2005 to September 2011. All men had CaP diagnosed on biopsy performed at our center, and elected AS over treatment. Failure was defined as progression to treatment. In men who failed AS, the reasons for failure, follow-up PSA and biopsy characteristics were analyzed. The primary outcome - time from diagnosis to failure of AS for a reason other than patient choice - was analyzed with univariable and multivariable Cox proportional hazards models. Results: In our AS cohort, 73% are Caucasian and 23% AA. Median follow-up is 25.4 months. Age, household income, BMI, PSA, clinical stage, family history, prostate volume, number of cores with cancer, and Gleason grade on initial biopsy did not differ by race. The number of biopsies and PSA tests performed on AS did not differ by race. A higher proportion of AA men tended to fail from biopsy progression (72.7% vs. 63.8%) while a lower proportion failed by choice (9.1% vs. 14.9%) compared to Caucasians (p = 0.114). AA men had a significantly shorter time to failure (HR 1.74, p = 0.045) compared to Caucasians. There was a trend toward increased Gleason grade 8 or higher cancer on follow-up biopsy in AA compared to Caucasian men (10% vs. 2.5%, p = 0.08). AA race remained a predictor (HR 1.76, p = 0.058) of failure on multivariable analysis, as did initial PSA (HR 1.90, p = 0.031) and number of cores with cancer on initial biopsy (HR 1.29, p = 0.013). Conclusions: AA race was associated with higher risk for failure of AS. There was a trend toward AA men failing due to biopsy progression and with higher grade cancer. Additional follow-up is necessary to determine how this affects the long term outcomes of these men.
Activity of oral VT-464, a selective CYP17-lyase inhibitor, in the LNCaP prostate cancer xenograft.
Authors: Figg William Douglas , Spencer Shawn D. , Pisle Stephen T , Pressler Heather M , Troutman Sarah M , Eisner Joel Robert , Rafferty Stephen W , Schotzinger Robert J , Moore William R 
Published: March 2020

4671 Background: With the FDA approval of abiraterone acetate, inhibition of CYP17 (17α hydroxylase/C17, 20-lyase) is now a validated approach to the treatment of castration-resistant prostate cancer. VT-464 is a novel, selective CYP17-lyase inhibitor with decreased activity against CYP17 hydroxylase (less mineralcocorticoid and glucocorticoid effects). The study objectives were to observe the effects of VT-464 in a prostate cancer xenograft model and to compare its activity to abiraterone acetate and surgical castration. Methods: SCID mice were implanted subcutaneously with LNCaP cells. When tumors reached 100 mm3, mice were randomized to receive vehicle (0.5% CMC in saline, 5 mL/kg), VT-464 at 15, 50, or 100 mg/kg p.o. b.i.d. A second cohort of LNCaP tumor-bearing mice received vehicle, surgical castration, or VT-464, or abiraterone acetate at 100 mg/kg p.o. b.i.d. for 28 days. Terminal blood and tumor concentrations were analyzed on day 28, four hours after the last dose. Results: In the first LNCaP xenograft cohort, percent growth inhibition (± S.E.) of 9.6 (±15.6), 38.5 (±12.4), and 73.9 (±13.2) was observed on day 21 of treatment for VT-464 doses of 15, 50, and 100 mg/kg, respectively. Growth reduction at 100 mg/kg was statistically significant compared to vehicle control from day 7 to 28. VT-464 was well tolerated with insignificant weight loss at all doses. In the second cohort, VT-464-treated (100 mg/kg) mice had significantly reduced tumor volumes on day 28 compared to control and abiraterone acetate (p<0.05, p<0.01, respectively). Reduction in tumor volumes were similar between VT-464-treated (100 mg/kg) and castrate animals. Plasma and tumor analyses revealed much greater plasma and tumor exposure of VT-464 compared to abiraterone acetate. Conclusions: VT-464 exhibited dose-dependent growth inhibition with significantly reduced tumor volumes at the highest dose compared to abiraterone acetate. The activity in VT-464-treated animals was similar to that of castrate animals. These preclinical results show promising activity of VT-464 in the treatment of prostate cancer.
KRAS and EGFR mutations to distinguish adenocarcinomas and squamous cell carcinomas of the cervix.
Authors: Wright Alexi A. , Hirsch Michelle S. , Wagle Nikhil , Howitt Brooke E , Palescandolo Emanuele , MacConaill Laura E. , Hummelen Paul Van , Shoni Melina , Hahn William C , Matulonis Ursula A 
Published: March 2020

5011 Background: Cervical adenocarcinomas (AC) have higher rates of recurrence and distant metastasis, compared with squamous cell carcinomas (SCC), and decreased survival in advanced disease. Yet, tailored treatments for cervical cancers have not emerged. The aim of this study was to compare the frequency and type of somatic mutations in cervical AC and SCC to identify novel therapeutic targets for both subtypes. Methods: Tumors from 61 patients with cervical cancer (36 AC, 25 SCC) underwent genomic profiling by OncoMap, a multiplexed mass spectrometric genotyping technology that interrogates more than 400 known mutations in 33 cancer genes. Results: Overall, 31/61 (50.8%) tumors harbored candidate mutations, and 6/61 (9.8%) had ≥2 mutations. PIK3CA mutations were present in 21/64 (34.4%) of cervical cancers, with a trend towards higher rates in SCC compared with ACC (21/25 or 48.0% vs. 9/27 or 33.3%, p=0.10). KRAS mutations were present in 6/31 (16.7%) of AC, but none of the SCC (0%; 0/25). EGFR mutations were present in 9/25 (36.0%) of SCC, including G719S, but none of AC (0%; 0/31). Conclusions: The identification of distinct genomic alterations in SCC and AC of the cervix suggest different therapeutic rationales for each subtype. EGFR amplification in cervical SCC has been previously reported, but this is the first identification, to our knowledge, of activating EGFR mutations in cervical SCC. Together, this suggests that EGFR-inhibitors might be useful in selected patients with cervical SCC. Similarly, activating mutations in KRAS and PIK3CA in AC suggest that inhibition of the MAPK pathway (MEK inhibitors) and/or PI3K pathway may be beneficial in this subtype. Future studies should include more comprehensive genomic profiling strategies, such as targeted massively parallel sequencing, to detect multiple types of genomic alterations.
Lenalidomide (REV) in asymptomatic late recurrent ovarian cancer (ROC) patients with increasing CA 125: A GINECO phase II trial.
Authors: Selle Frédéric , Ray-Coquard Isabelle , Sevin Emmanuel , Mari Véronique , Berton-Rigaud Dominique , Bourgeois Hugues Pierre , Dohollou Nadine , Fabbro Michel , Floquet Anne , Lesoin Anne , Lortholary Alain , Hardy-Bessard Anne-Claire , Misset Jean-Louis , Mouret-Reynier Marie-Ange , Pujade-Lauraine Eric 
Published: March 2020

5018 Background: REV is a thalidomide analogue, with both immunomodulatory and anti-angiogenic properties that could confer antitumor effect in ROC. Methods: The aim of this study was to evaluate REV efficacy as single agent in patients (pts) with asymptomatic late ROC (>6mos) with increasing CA 125, in 2nd or 3rd line. Primary endpoint was to estimate the rate of non-progressive disease at 4 mos. Pts were treated with REV 20 mg daily in oral continuous regimen with systematically recommended anti-thrombotic prophylaxis (ATP). Imagery and CA 125 were performed every 8 weeks. Results: From 05/2009 to 09/2010, 45 pts were included with a median age of 63 years. Pt characteristics were: serous (78%), previous lines (one 73%, two 27%), median platinum-free interval (PFI) (11.3 mos), PFI > 12 mos (42%), measurable disease (73%), and ECOG performance status 0 (84%). Efficacy: Rate of non progressive disease at 4 mos was 38% (95%CI, 23-53), 59 % (95%CI, 36-82) and 24 % (95%CI, 7-41) for the global population, pts relapsing over 12 mos and those relapsing between 6-12 mos, respectively. Results were independent of the number of previous lines. Median progression-free survival was 3.8 mos (95%CI, 2.1-5.6) and 6.4 mos in the subset of pts with PFI > 12 mos. Response evaluation according to CA 125 (Rustin criteria) was: complete response (CR) 2.4%, partial response (PR) 17%, stable disease (SD) 71%. When using RECIST criteria alone, response evaluation was: 9.5% PR and 45% SD. Median duration of biological response was 6.6 mos. REV efficacy will be correlated to immunological parameters (lymphocyte phenotypes and cytokines). Safety: Grade 3-4 toxicity in more than 5% of pts was neutropenia (29%) and thrombo-embolic events (TEE) (11%). TEE occurred only in pts without ATP. Reasons for stopping treatment due to toxicity were TEE (3), allergy (2), arrhythmia (1), dyspnea (1) and neutropenia (1). Conclusions: REV demonstrated encouraging activity in ROC with good tolerability and manageable adverse events. A phase I of REV combined with platinum-based chemotherapy is currently being conducted.
A phase II study of RO4929097 (RO), a gamma-secretase inhibitor, in advanced platinum (Pt)-resistant (R) ovarian cancer (OC): A study of the PMH, Chicago, and California phase II consortia.
Authors: Diaz-Padilla Ivan , Clarke Blaise A , Hirte Hal W. , Welch Stephen , Mackay Helen , Biagi James Joseph , Reedijk Michael , Weberpals Johanne Ingrid , Fleming Gini F. , Wang Lisa , Li Jennifer , Strevel Elizabeth Laureen , Eisenhauer Anne , Ivy S. Percy , Oza Amit M. 
Published: March 2020

5019 Background: Notch signalling pathway plays a critical role in regulating cellular differentiation, proliferation, and apoptosis in preclinical cancer models. The Notch receptor, its ligands, and down-stream effectors are over-expressed in OC. Inhibition of γ-secretase-mediated Notch cleavage is a primary focus for the development of targeted therapeutics. Methods: Women (pts) with progressive, measurable (RECIST), Pt-R OC treated with ≤ 2 chemotherapy regimens for recurrent disease were treated with oral RO at 20mg od, 3 days on/4 days off every week, q3w. The primary objective was to determine the antitumor efficacy of RO in Pt-R OC by the progression-free survival (PFS) rate at the end of 4 cycles. Secondary objectives were to assess the safety of RO and to explore molecular correlates of outcome in archival tumor tissue. A Simon two-stage design was used. The study would open to second stage accrual if > 4 pts of the first 17 accrued remain progression-free at the end of 4 cycles. Results: 39 pts have been enrolled after first-stage criteria were met. Median age was 59 (range 26-81). Median number of cycles was 2 (range 1-18). 30 (83%) pts had high-grade serous OC. 34 pts were evaluable for response. 8 pts (20%) were progression-free after 4 cycles.12 pts (35%) had stable disease, with a median duration of 3.9 months (range 2.5-12.2). Median PFS was 1.3 months (1.2-2.3). The most common drug-related adverse events (AEs) of any grade (% pts) were: nausea (36), fatigue (28), anorexia (15), hypophosphatemia (15), anemia (13), and increased alanine aminotransferase [ALT] (13). There were 5 G3-4 AEs at least possibly related with RO: increased liver transaminases (2), diarrhea (1), headache (1), and hypophosphatemia (1). Intracellular Notch (NIC) and JAG1 protein expression on high-grade serous OC were correlated with response in 17 pts. Median PFS for pts with high NIC (n=6) was 3.3 months (1.0-not reached), compared to 1.3 months (1.1-2.6) for pts with low NIC (n=11), p=0.09. Conclusions: RO has limited clinical activity in unselected Pt-R OC as a single agent. Future studies need to assess potential for cohort enrichment using NIC expression.
Brief family history questionnaire for identification of Lynch syndrome in women with newly diagnosed endometrial cancer.
Authors: Ferguson Sarah E , Clarke Blaise , Mojtahedi Golnessa , Oza Amit M. , Gallinger Steve , Pollett Aaron , Mackay Helen , Bernardini Marcus , Aronson Melyssa 
Published: March 2020

5026 Background: Endometrial cancer (EC) is often the sentinel cancer for women with Lynch syndrome (LS); however, it is underappreciated in this population. The Brief Family History Questionnaire (bFHQ) was developed to identify women with EC who have family histories suggestive of LS. The objective of our study was to evaluate the bFHQ compared to an extended family history (eFHQ) and medical record in identifying women with EC who may benefit from genetic cancer risk assessment. Methods: All women with newly diagnosed EC from July 2010 to June 2011 were asked to participate in a prospective screening protocol for LS which included completing two family history questionnaires; the bFHQ which is a 4-item self-report measure and the 37-item eFHQ administered by a research assistant. Family history was also extracted from the medical record. Using the bFHQ women were flagged as requiring additional investigation for LS based on predetermined criteria and the predictive ability of the flag was evaluated treating eFHQ as the gold standard. Comparisons were made between the bFHQ, eFHQ and medical record for families meeting Amsterdam II, Society Gynecologic Oncologist (SGO) 20-25% or the Ontario Ministry of Health (MOH) testing criteria for LS, using generalized estimating equation logistic regression models. Results: 119 (N = 182, 65%) consented to the study and 106 (89%) completed the bFHQ. The median age was 61 (26-91). The number of women who met testing criteria by the eFHQ was 17 (16%) and 33 (31%) were flagged by the bFHQ. The sensitivity, specificity, PPV and NPV of the bFHQ was 88.2%, 79.8%, 45.5% and 97.3%. There was no significant difference in the number of women who met Amsterdam II or SGO 20-25% testing criteria between the bFHQ, eFHQ and medical record (P > 0.05). The numbers of women meeting MOH criteria using the bFHQ (N=16, 15%) and the eFHQ were similar (N=17, 16%) (P = 0.7); however, more women met MOH criteria using the bFHQ and the eFHQ compared to the medical record (N=8, 7.6%) (P = 0.011; P = 0.006). Conclusions: The patient-administered bFHQ is a highly effective tool in identifying women who meet MOH testing criteria for LS and is a good screening tool to identify women with EC for further genetic assessment.
Correlative study of low serum creatinine and hematological toxicities in Japanese patients with ovarian cancer treated by dose dense TC therapy.
Authors: Matsumoto Koji , Onoe Takuma , Kitao Akihito , Tanioka Maki , Negoro Shunichi 
Published: March 2020

5045 Background: Dose dense TC (ddTC) is a novel standard therapy for patients (pts) with advanced ovarian cancer, although hematological toxicities (hemTX), especially anemia, may increase as observed in NOVEL trial (JGOG3016). Low serum creatinine (LCr), especially below 0.7 mg/dl, may lead to overestimation of GFR. GOG announced that pts with LCr should use a minimum value of 0.7mg/dl to estimate GFR. The correlation between LCr and hemTX treated by ddTC is unknown. Methods: GFR was determined using the Cockcroft-Gault formula. Serum creatinine concentrations were measured using enzymatic assays. Minimum value of 0.7 mg/dl was not used during this period of time. The carboplatin clearance was then calculated by Calvert equation. HemTX were defined as, Grade 3 or 4 (by CTC-AE ver.4) neutropenia, anemia, and thrombocytopenia. Using electrical chart, frequency of hemTX and correlation between serum creatinine (less than 0.7 or not) were examined. Results: From Feb. 2010 to Dec. 2011, 61 consecutive pts were treated with ddTC. LCr was observed in 73% of pts. No treatment related death occurred. Among 61 pts, 50 (82%), 31 (51%), and 12 (19.6 %) pts experienced Grade3/4 neutropenia, anemia and thrombocytopenia, respectively. HemTX in pts with LCr and the others were as in the Table. Conclusions: LCr is frequent in Japanese female pts. ddTC in practice setting seems safe, and hemTX of ddTC are similar with those observed in NOVEL trial. The rationale using a minimum value of 0.7 mg/dl should be further studied by larger population, such as pts in NOVEL trial. [Table: see text]