bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 17-gene panel for prediction of adverse surgical pathology in the setting of MRI-guided prostate biopsy.
Authors: Salmasi Amirali , Said Jonathan W. , Raman Steven , Shindel Alan W , McCullough Debbie , Bailey Helen , Rothney Megan , Marks Leonard S. , Febbo Phillip G. , Reiter Robert Evan 
Published: September 2018

5063 Background: A 17 gene panel (Oncotype Dx Genomic Prostate Score, GPS) has been validated as an independent predictor of adverse pathology (AP, defined as pathological GS 4+3 or higher and/or pT3+) in men treated with radical prostatectomy (RP) for prostate cancer (PCa). Multiparametric Magnetic Resonance Imaging (mpMRI) may help guide prostate biopsies. We explored synergies between GPS and mpMRI to aid in PCa management decisions. Methods: A cohort of men with NCCN Low and Intermediate-Risk PCa who were managed with RP was identified from a clinical database. Patients were required to have had a simultaneous mpMRI-guided and systematic biopsy and to have undergone RP within 6 months. Biopsy tissue of the highest Gleason pattern was used for calculation of GPS. The primary endpoint was AP. Secondary endpoints included the range of GPS within UCLA prostate MRI risk groups and median GPS when there was discrepancy between MRI and systematic biopsy Gleason Score (GS). Logistic regression models were fit to evaluate the relationship between GPS (per 20 units) and AP. Results: 134 men met criteria for the primary endpoint. Median age was 62 years (range 46-77). NCCN Low & Intermediate-Risk PCa was present in 16%, and 84% of men, respectively. Biopsy GS 3+3/3+4/4+3 was present in 19%, 67%, and 13%, respectively. In a univariable model, GPS was associated with AP (OR 3.8, 95% CI 2.1 to 7.4, p < 0.001). After adjustment for highest biopsy GS and clinical T-stage, GPS remained significantly associated with AP (OR 3.4, 95% CI 1.8 to 6.8, p = 0.0004). A wide and overlapping distribution of GPS was noted across UCLA MRI prostate risk groups, indicating that GPS provides information that is distinct from what can be determined from mpMRI. When there was a discrepancy between mpMRI and systematic biopsy GS, mpMRI targeted lesions with higher GS had higher median GPS (33, range 13-70) than systematic biopsies with higher GS (median GPS 25, range 15-55). Conclusions: GPS provides independent and complementary prognostic information to mpMRI-guided biopsies. The combination of mpMRI for biopsy guidance and GPS for molecular analysis may optimize prediction of AP and improve patient selection for treatment versus surveillance.
The accuracy of multiparametric magnetic resonance imaging (mpMRI) using PI-RADS v2 in disease upgrading on re-biopsy among patients with low-risk prostate cancer (PCa) on active surveillance (AS): A Brazilian perspective.
Authors: Viana PÃºblio C. C. , Horvat Natally , Guglielmetti Giuliano , Coelho Rafael , Nahas William Carlos , Park Rubens , Bezerra Regis , Bastos Diogo Assed , Rodrigues Thiana , Vargas Hebert Alberto 
Published: September 2018

5084 Background: The current selection criteria to AS is critical and it becomes even more relevant in Latin America, given the higher proportion of high risk cancers. The objective of this study is to analyze the accuracy of mpMRI using PI-RADS v2 in predicting the risk of upgrading on re-biopsy (UR) in men with low-risk PCa on AS. Methods: In this Institutional Review Board approved prospective study, patients with low-grade PCa selected for AS at our institution underwent mpMRI at least 6 weeks after the baseline 12-core random prostate biopsy (BSB), from March 2014 to March 2016. One blinded abdominal radiologist evaluated the exams regarding presence of dominant lesion and assigned the PI-RADS v2 score. MRI-target transrectal ultrasound-guided re-biopsies were performed in all patients within 6-12 months after the BSB. Standardized 12-core biopsy was performed and additional cores were taken from suspicious areas on mpMRI. Results: One hundred and nine patients were included, 93 (85.3%) patients had a dominant lesion on MRI. mpMRI were classified as PI-RADS 1, 2 or 3 in 67 (61.5%) patients, and as PI-RADS 4 or 5 in 42 (38.5%) patients. UR occurred in 42 (38.5%) patients. Out of these, 39 (92.8%) had radical prostatectomy, 6 (15.4%) T2a, 24 (61.5%) T2b, and 9 (23.1%) T3a. The diagnostic performance of mpMRI for PCa upgrading after re-biopsy was summarized in table 1. Patients assigned as PI-RADS 4 or 5 presented a significantly higher risk for UR compared with patients with PI-RADS 1, 2 or 3 (73.8% vs 16.4%, p < 0.001). Logistic regression analyses demonstrated that PI-RADS 4 or 5 remained a significant predictor of UR (OR: 37.366, p < 0.0001). Conclusions: We demonstrated in our population that mpMRI using PI-RADS v2 is a significant predictor for upgrading on re-biopsy in patients on AS and could be used to guide TRUS biopsy, increasing the accuracy of current clinical criteria for AS. [Table: see text]
Multi-institutional comparison of breast cancer risk stratification by 70-gene signature and 21-gene assay.
Authors: Dabbs David J. , Cox Charles E. , Shivers Steven , Bouganim Nathaniel , Asselah Jamil , Saleh Ramy , Blumencranz Lisa Eileen , Montero Alberto J. , Calhoun Benjamin C. , Treece Tina , Yoder Erin , Audeh William 
Published: September 2018

522 Background: Breast cancer risk stratification with the 70-gene signature (70-GS) provides a binary low risk (LR) or high risk (HR) result; by contrast the 21-gene assay (21-GA) provides LR, intermediate (IR), and HR results. Results from these two assays were compared for 769 patients from 5 institutions. Methods: The study included patients from McGill University (n = 86), UPMC (n = 437), USF (n = 135), Morton Plant North Bay Hospital (n = 79), and Cleveland Clinic (n = 32, all 21-GA IR). Results: With the 70-GS, 487 (63%) patients had a LR and 282 (37%) patients had a HR result. Excluding 32 cases selected for 21-GA IR results (n = 737), the 21-GA gave 369 (50%), 250 (34%), and 118 (16%) patients with LR, IR, and HR scores, respectively. Using the TAILORx cutoff, there were 134 (18%), 432 (59%), and 171 (23%) patients with LR, IR, and HR scores, respectively. There were 329 (45%) and 486 (66%) patients who were not classified in the same risk category by both assays using the clinical and TAILORx cutoffs for IR, respectively. Conclusions: In a large multi-institutional study the 70-GS and 21-GA results were discordant in 45-66% of patients, and the proportion of patients with a 21-GA score in the IR range varied from 34-59%. The 70-GS provided clinically actionable results for all patients. [Table: see text]
Copy-number and targeted sequencing analyses to identify distinct prognostic groups: Implications for patient selection to targeted therapies amongst anti-endocrine therapy resistant early breast cancers.
Authors: Bayani Jane , Kornaga Elizabeth , Crozier Cheryl , Jang Gun Ho , Kalatskaya Irina , Trinh Quang M , Yao Cindy Q , Livingstone Julie , Hasenburg Annette , Kieback Dirk G , Markopoulos Christos , Dirix Luc , Boutros Paul Christopher , Spears Melanie , Stein Lincoln D. , Rea Daniel , Bartlett John 
Published: September 2018

524 Background: Hormone receptor positive breast cancer is a therapeutic challenge. Despite optimal anti-endocrine therapies, most breast cancer deaths follow a diagnosis of early luminal cancer. To understand the impact of multiple aberrations in the context of current therapy, we assessed the prognostic ability of genomic signatures as a putative stratification tool to targeted therapies. Methods: This a priori study is based on molecular pathways which might predict response to targeted therapies. DNA from 420 patients from the phase III TEAM pathology cohort were used. Patients with a distant recurrence within 5 years were matched by clinical variables to those disease-free at follow up. Copy number analysis was performed using the Affymetrix Oncoscan Assay. Targeted sequencing was performed in a subset of samples for genes based on signaling cassettes mined from the ICGC. Pathways were identified as aberrant if there were copy number variations (CNVs) and/or mutations in any of the pre-determined pathway genes: 1) CCND1/CCND2/CCND3/CDK4/CDK6; 2) FGFR1/FGFR2/FGFR2/FGFR4; and 3) AKT1/AKT2/PIK3CA/PTEN. Kaplan-Meier and log-rank analyses were used for DFS between groups. Hazard ratios were calculated using the Cox proportional hazard models adjusted for age, tumour size, grade, lymph node and HER2 status. Results: 390/420 samples passed informatics QC filters. For the CCND/CDK pathway, patients with no CNV changes experienced a better DFS (HR = 1.7, 95% CI 1.3-2.3, p < 0.001). For the FGFR/FGF pathway, a similar outcome is seen among patients without CNVs (HR = 1.5, 95% CI 1.1-2.0; p = 0.005). For AKT/PIK3CA, a decrease in DFS was seen in those with aberrations (HR = 1.4, 95% CI 1.0-1.8, p = 0.03). Conclusions: We demonstrated that CNVs of genes within CDK4/CCND, PIK3CA/AKT and FGFR pathways are independently linked to high risk of relapse following endocrine treatment, with implications for identifying those patients who are at high-risk for recurrence despite optimal anti-endocrine therapy and linking molecular features driving these cancers to targeted therapies.
Overall survival results of ICON6: A trial of chemotherapy and cediranib in relapsed ovarian cancer.
Authors: Ledermann Jonathan A. , Embleton Andrew C. , Perren Timothy , Jayson Gordon C. , Rustin Gordon J. S. , Kaye Stanley B. , Hirte Hal W. , Oza Amit M. , Vaughan Michelle Margaret , Friedlander Michael , Gonzalez Martin Antonio , Clark Elizabeth , Popoola Babasola O , Farrelly Laura , Swart Ann Marie , Cook Adrian , Kaplan Richard S. , Parmar Mahesh K B ,   ICON6 Collaborators
Published: September 2018

5506 Background: ICON6 is a three-arm double-blind, placebo-controlled phase 3 trial of cediranib in platinum-sensitive relapsed ovarian cancer (NCT00532194). The primary analysis (Ledermann et al Lancet 2016) showed a significant (p < 0.0001), 2.3 month extension in progression-free survival (PFS) using cediranib with chemotherapy and as maintenance compared to chemotherapy and placebo. We present the final overall survival (OS) results. Methods: The trial was originally designed to recruit 2000 patients with OS as the primary endpoint. AstraZeneca discontinued cediranib development in Sep 2011, leading to an unplanned redesign prior to analysis. The sample size was reduced and primary outcome became PFS, comparing two arms, placebo (A) to cediranib given with chemotherapy and as maintenance (C). In arm B cediranib was given with chemotherapy followed by placebo maintenance. Analysis of PFS was performed on a sample size of 456 patients receiving a 20mg dose of cediranib. At the primary analysis, 52% patients had died; this mature OS analysis was performed after 85% patients died. Results: The OS analysis was performed at a median 25.6 months follow up; 102/118 (86%) died in A and 140/164 (85%) in C. In A the median survival was 19.9 months (95% CI: 17.4, 26.5) and in C 27.3 months (24.8, 33.0). Using the logrank test the Hazard Ratio estimate was 0.85 (0.66, 1.10) in favour of cediranib (p = 0.21). Evidence of non-proportionality of the survival curves was observed (p = 0.0029), so we measured the Restricted Mean Survival Time as an alternative to the median. Over 6 years, there was a 4.8 month (-0.1, 9.8) increase in time to death in C compared to A, from 29.4 to 34.2 months. The mean for arm B (32.0 months) was consistent with a benefit of increased use of cediranib. Conclusions: Cediranib has demonstrated a significant effect in increasing PFS. The mature survival analysis (85%) shows an improvement in median OS of 7.4 months, and an incremental benefit with increased cediranib use. The previously published significant PFS benefit coupled with the increase in OS highlights the potential value of cediranib in platinum-sensitive recurrent ovarian cancer. Further exploration of cediranib in this setting is underway. Clinical trial information: NCT00532194.
Adverse events (AEs) with maintenance olaparib tablets in patients (pts) with BRCA-mutated (BRCAm) platinum-sensitive relapsed serous ovarian cancer (PSR SOC): Phase III SOLO2 trial.
Authors: Ledermann Jonathan A. , Lortholary Alain , Penson Richard T. , Gibbs Emma , Provencher Diane M. , Bruchim Ilan , Huzarski Tomas , Barretina-Ginesta Maria Pilar , Sabbatini Roberto , Mileshkin Linda R. , Colombo Nicoletta , Park-Simon Tjoung-Won , Matsumoto Koji , Sonke Gabe S. , Mikheeva Olga N. , Kim Jae-Weon , Girotto Gustavo Colagiovanni , Denys Hannelore , Lowe Elizabeth S. , Pujade-Lauraine Eric 
Published: September 2018

5518 Background: In the SOLO2 trial (ENGOT Ov-21; NCT01874353), maintenance therapy with the PARP inhibitor olaparib significantly improved PFS vs placebo (PBO) in BRCAm PSR SOC pts (HR 0.30, 95% CI 0.22–0.41, P<0.0001; median 19.1 vs 5.5 months) and was well tolerated (Pujade-Lauraine et al, SGO 2017). We analyzed AEs in SOLO2, the first study in PSR SOC to use the olaparib tablet formulation. Methods: Pts with BRCAm PSR SOC, who were in response to platinum chemotherapy, were treated with olaparib (300 mg bid; tablets; n=195) or PBO (n=99) until progression. AEs were graded by CTCAE v4.0. Results: The most common AEs with olaparib – nausea, fatigue/asthenia, anemia, and vomiting – were largely grade 1–2, though anemia was the most common grade ≥3 AE. AEs of fatigue/asthenia, vomiting and nausea generally improved as treatment continued, though fatigue/asthenia and anemia could last for several months (table). Most AEs were manageable by supportive treatment, dose interruptions (olaparib, 45%; PBO, 18%) and dose reductions (olaparib, 25%; PBO, 3%). Discontinuation of olaparib due to AEs was minimal (11%); anemia and neutropenia were the only AEs leading to discontinuation of olaparib in >one pt. Conclusions: Most AEs experienced by pts receiving olaparib tablets in SOLO2 were low grade and manageable. Initial nausea, vomiting and fatigue generally improved with ongoing treatment. The majority of AEs first occurred within the first three months of treatment. AEs causing treatment discontinuation were rare and mainly hematological. Clinical trial information: NCT01874353. [Table: see text]
Effect of denosumab on bone mineral density (T-score classification of −1.0 to −2.5) in postmenopausal Japanese women receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer.
Authors: Nakatsukasa Katsuhiko , Matsuda Takayuki , Taguchi Tetsuya 
Published: September 2018

552 Background: Adjuvant aromatase inhibitor (AI) therapy is well established in postmenopausal women with hormone receptor-positive breast cancer, but such therapy is associated with bone loss and increased fracture risk. Denosumab, a fully human monoclonal antibody against receptor of nuclear-κB ligand, was previously proven to protect against AI-induced bone loss. In Japan, however, the efficacy of denosumab in the treatment of AI-associated bone loss has not been proven in a prospective study. Methods: This non-randomized prospective study was conducted at four institutions in Japan. we prospectively evaluated the bone mineral density (BMD) of the lumbar spine and bilateral femoral neck in hormone-receptor positive clinical stageⅠ–ⅢA, postoperative postmenopausal breast cancer patients who were scheduled for treatment with AI as adjuvant endocrine therapy or during AI adjuvant therapy. They received supplemental calcium, vitamin D and subcutaneous denosumab 60mg (n=103) every six months. At enrollment, all patients were required to have evidence of low bone mass, excluding osteoporosis. The primary endpoint was percentage change in lumbar spine BMD from baseline to month 12. The secondary endpoint was percentage change in bilateral femoral neck BMD from baseline to month 12. This is the first trial where the right and left femoral neck BMD are measured separately. Results: We enrolled 103 patients between November, 2014 to October, 2016. At 12 months, lumber spine BMD increased by 4.7 %. The patients who were administered prior AI therapy (n=60) had a 4.8 % increase, and the patients without prior AI therapy (n=40) had a 4.6 % increase. At 12 months, the right and left femoral neck BMD increased by 2.9 % and 2.0 %, respectively. Hypocalcemia ≥ grade2, osteonecrosis of the jaw (ONJ) and non-traumatic clinical fracture were absent in this study. Conclusions: Twice-yearly treatment with denosumab was associated with consistently greater gains in BMD among Japanese women receiving adjuvant AI therapy, regardless of whether prior AI therapy was administered. Clinical trial information: UMIN000013863.
Stage I ovarian immature teratomas: Is there a role for chemotherapy?
Authors: Chan John K. , Rosenfeld Emily B , Gardner Austin Blake , Delic Lejla , Kapp Daniel Stuart 
Published: September 2018

5523 Background: To determine the impact of chemotherapy on survival of patients with stage I ovarian immature teratomas. Methods: Data obtained from the National Cancer Database from 2004-2013. Kaplan-Meier methods and multivariate Cox regression models were used for statistical analyses. Results: Of 888 patients (median age 24 years), 76%, 7%, 15%, 3% were stages I, II, III, and IV, respectively. 27%, 28%, 38%, and 8% had grades 1, 2, 3 and 4. The predominant racial group was White (50%) and remainder Black (19%), Hispanic (16%), Asian (6%) and other (9%). 64% had fertility sparing surgery and 55% received chemotherapy. For all patients, 5 year survival was over 90%. Chemotherapy did not change the 5 year survival for stage I or stage II disease (p = 0.35 and p = 0.69, respectively). However, chemotherapy improved 5 year survival from 59% to 76% in stages III-IV (p < 0.01). When controlling for other factors, older age (HR 3.2, p < 0.01), stages II and III-IV (HR 6.0, p < 0.01; HR 10.6, p < 0.01) and grades 3-4 (HR 15.3, p < 0.01) had worse survival. In a subset analysis of stage I patients chemotherapy did not improve 5 year survival of those with stage I grade 1 (p = 0.75) but chemotherapy did improved the survival of those with stage I grade 2 disease from 85% to 99% (p = 0.04). Conclusions: The overall survival of patients with immature teratomas is excellent. In patients with stage I grade 2 or higher disease chemotherapy was associated with an improved overall survival.
A randomized phase II study assessing an optimized schedule of oregovomab (O) anti-CA125 vaccination with carboplatin paclitaxel (CP) relative to CP alone in front-line treatment of optimally cytoreduced stage III/IV ovarian cancer (EOC).
Authors: Ferrandina Gabriella , Braly Patricia S. , Terranova Corrado , Salutari Vanda , Ricci Caterina , Raspagliesi Francesco , Lorusso Domenica , Panici Pierluigi Benedetti , Scollo Paolo , Plotti Francesco , Brewer Molly , Method Michael W. , Holloway Robert W. , Madiyalakan Madi , Nicodemus Christopher F. , Pecorelli Sergio L. , Scambia Giovanni , Angioli Roberto 
Published: September 2018

5536 Background: In a phase II study of vaccination schedule in front-line combinatorial treatment of EOC (Braly JIT 2009), simultaneous day infusion dramatically enhanced the magnitude of induced immunity relative to a one week delayed schedule & other schedules historically evaluated. The current study is exploring the clinical & biological effects of the optimized 4 vaccine schedule relative to CP alone. Methods: Stage III/IV EOC patients (pts) optimally debulked to <1cm residual disease with CA125 >2x ULN were randomized to CP+O (cycle 1,3,5, & C5 +12 weeks) vs CP and followed for clinical outcomes and immune reponse. A total of at least 80 evaluable pts were required for 80% power to detect a difference of 45% vs 15% for a primary comparative analysis of induced CA125 specific T cell immunity using an IFN-γ ELISpot. Clinical evaluations and safety were considered secondary endpoints. Results: 97 pts (47 OV+SOC & 50 SOC) were accrued at 13 centers in US & Italy. Analysis of immune markers and long term clinical outcomes is ongoing. The median duration of follow up at time of this analysis was 26 months (m). There was no difference in safety outcomes between the treatment groups. Grade 3-4 toxicity was observed in 24 (52%) CP+O vs 28 (58%) C-P pts. Toxicities were typical of standard IV C-P chemotherapy. K-M Analysis of recurrence free survival (RFS) showed median RFS not estimable for CP+O [95% CI: 21.3, NE] vs 15.4 m [10.9,19.3] for CP (p=0.0009 log rank). In the interim analysis of survival (OS), 4 deaths have been observed in CP+O vs 16 in CP (log rank p=0.0025). Cox proportional hazard analysis finds consistent results across centers, and no imbalance in identified risk factors explanatory for the emerging outcome Conclusions: This study suggests simultaneous day vaccination with O on alternate cycles of front line CP leverages CP associated temporal change in the tumor microenvironment permitting an immune treatment effect to enhance the outcomes achievable with CP alone. This observation will be further characterized in ongoing translational studies and confirmed in a future phase III study. Clinical trial information: NCT01616303.
Mirvetuximab soravtansine (IMGN853), a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in platinum-resistant epithelial ovarian cancer (EOC) patients (pts): Activity and safety analyses in phase I pooled expansion cohorts.
Authors: Moore Kathleen N. , Matulonis Ursula A. , O'Malley David M. , Konner Jason A. , Martin Lainie P. , Perez Raymond P. , Bauer Todd Michael , Gilbert Lucy , Seward Shelly Marie , Oza Amit M. , Ruiz-Soto Rodrigo , Birrer Michael J. 
Published: September 2018

5547 Background: The early clinical evaluation of mirvetuximab soravtansine (IMGN853), an ADC that comprises a FRα-binding antibody linked to the tubulin-disrupting maytansinoid DM4, has revealed encouraging signs of activity in pts with ovarian cancer. A pooled analysis of safety and efficacy was performed including individuals with platinum-resistant EOC, enrolled across three expansion cohorts of an ongoing phase I trial (NCT01609556), who met the eligibility criteria for the pivotal phase III study of IMGN853 (FORWARD I; NCT02631876). Methods: Pts were administered IMGN853 intravenously once every 3 weeks at 6 mg/kg using adjusted ideal body weight dosing. Responses were assessed according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.0. Results: A total of 37 EOC pts treated as part of the three phase I expansion cohorts (pooled population; n = 113) met the FORWARD I enrollment criteria of moderate to high tumor FRα levels (≥ 50% of cells with ≥ 2+ FRα expression) and 1-3 prior lines of therapy. In this group of pts with platinum-resistant disease, confirmed objective tumor responses were observed in 17 individuals (1 complete response [CR] and 16 partial responses [PR]) for an overall response rate (ORR) of 46% (95% CI, 29.5, 63.1) and a median PFS of 6.7 months (95% CI, 4.1, 9.0). The safety profile of the pooled population was consistent with that previously reported (ASCO Annual Meeting, 2016) with the most common AEs being diarrhea, fatigue, nausea, and blurred vision; these were low grade and readily managed. Conclusions: IMGN853 continues to be characterized by favorable tolerability and encouraging activity in pts with platinum-resistant EOC. In particular, both the ORR (46%) and PFS (6.7 months) achieved in this group of pts are superior to outcomes typically seen with established single-agent chemotherapy within the setting of primary platinum resistance. Overall, these analyses provide continued, robust support for the patient eligibility strategy employed in the phase III evaluation of IMGN853. Clinical trial information: NCT01609556.